PMPGCF PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS FISIOLÓGICAS (PMPGCF) INSTITUTO MULTIDISCIPLINAR EM SAÚDE Téléphone/Extension: Indisponible
Dissertation/Thèse

Clique aqui para acessar os arquivos diretamente da Biblioteca Digital de Teses e Dissertações da UFBA

2024
Thèses
1
  • LARA FABIANA LUZ MALHEIRO
  • High-intensity interval training regulates hepatic inflammation through the TLR4/NF-κB signaling pathway in rats with cisplatin hepatotoxicity. 

  • Leader : LILIANY SOUZA DE BRITO AMARAL
  • MEMBRES DE LA BANQUE :
  • LILIANY SOUZA DE BRITO AMARAL
  • AMELIA CRISTINA MENDES DE MAGALHAES GUSMAO
  • RAILDO DA SILVA COQUEIRO
  • Data: 21 févr. 2024


  • Afficher le Résumé
  • Cisplatin (CP) is a chemotherapy agent widely used to treat various types of solid tumors. However, its lack of selectivity affects healthy cells, causing several cytotoxic effects, including hepatotoxicity. Although the underlying mechanisms of hepatotoxicity are not fully understood, evidence suggests a significant involvement of the inflammatory process, in which increased expression of pro-inflammatory cytokines, reduction of anti-inflammatory cytokines, and immune cell infiltration are determinants in the exacerbation and progression of tissue damage. Recently, some studies have reported the hepatoprotective effects mediated by regular aerobic physical exercise. However, it is still unclear which intensity is most effective in enhancing these protective effects, especially in acute liver injuries. Therefore, this study aims to compare the impacts between preconditioning with high-intensity interval training (HIIT) and traditional continuous training of light (LIT) and moderate (MIT) intensities on inflammatory markers in Wistar rats with CP-induced hepatotoxicity. For this purpose, 35 Wistar female rats were divided into five groups (n=7 in each group): control and sedentary (C+S); treated with CP and sedentary (CP+S); treated with CP and subjected to LIT (CP+LIT); treated with CP and subjected to MIT (CP+MIT); and treated with CP and subjected to HIIT (CP+HIIT). The training protocols consisted of treadmill running, 5 days a week, for 8 weeks before the CP treatment. At the end of the 8-week training period, the rats received a single injection of CP (5 mg/kg i.p) or saline, and 7 days after the injection, they were euthanized. Liver samples were collected to evaluate the expression of nuclear factor kappa B (NF-κB), toll-like receptor 4 (TLR4), tumor necrosis factor alpha (TNF-α), interleukin (IL)-1α, IL-1β, IL-6, IL-8, and IL-10, the number of ED-1 positive cells, and M1 (iNOS) and M2 (arginase) macrophages markers in the hepatic tissue. Our results indicate that HIIT was the only exercise protocol capable of preventing the increase in all analyzed pro-inflammatory cytokines and reducing the number of ED-1 positive cells, at least in part through attenuating the TLR4/NF-κB signaling pathway. Additionally, preconditioning with HIIT enhanced the expression of the anti-inflammatory cytokine IL-10 and the M2 macrophage marker while reducing the expression of the M1 macrophage marker in hepatic tissue. Thus, this study suggests that preconditioning with HIIT is more effective in promoting hepatoprotective effects than LIT and MIT preconditioning protocols, regulating important inflammatory markers through modulation of the TLR4/NF-κB signaling pathway in the hepatic tissue of female rats treated with CP.

2
  • JÚLIA DE OLIVEIRA BORGES
  • EFFECTS OF DIETARY COMPOSITION AND/OR PHYSICAL TRAINING ON IRISIN CONCENTRATION AND MORPHOFUNCTIONAL PARAMETERS OF ADIPOSE TISSUE IN OBESE WISTAR RATS

  • Leader : RAFAEL PEREIRA DE PAULA
  • MEMBRES DE LA BANQUE :
  • RAFAEL PEREIRA DE PAULA
  • AMELIA CRISTINA MENDES DE MAGALHAES GUSMAO
  • TELMA DE JESUS SOARES
  • Luciano Evangelista dos Santos Filho
  • Data: 27 févr. 2024


  • Afficher le Résumé
  • Objective: To evaluate the effects of physical training and a carbohydrate-restricted and high-protein diet on the modulation of plasma and muscle irisin and morphological and functional changes in white and brown adipose tissue of male Wistar rats in an obesity model. Methods: 40 male Wistar rats were divided into two groups: Control group (n=6) and Group with a high-calorie diet (HC) to induce obesity (n=34) for 8 weeks. After this period, 6 animals from each group were euthanized to confirm obesity. Then, the obese animals were divided into 4 groups: Group submitted to the HC diet and sedentary (n=7); Group submitted to the HC diet and trained (n=7); Group submitted to a high-protein, carbohydrate-restricted
    (HP) diet and sedentary; Group submitted to a high-protein and carbohydrate-restricted diet (HP) and trained (n=7). After a period of 12 weeks, the animals were euthanized and the subcutaneous, epididymal and brown adipose tissues, as well as muscle tissue and thoracic blood were collected for further analysis. Body composition, serum and tissue modulation of irisin/FNDC5, morphology of the gastrocnemius muscle and subcutaneous (TASC) and brown (TAM) adipose tissues were evaluated. Mitochondrial activity and energy metabolism parameters in TASC and TAM and inflammatory markers, oxidative damage and antioxidant enzyme activity in TASC, TAE and TAM were also evaluated.Statistical analyzes were performed using the two-way ANOVA test (2 diets x 2 training conditions), followed by the Bonferroni post-test. Data were presented as mean±standard error. Results: The HP diet and physical training positively influenced body composition parameters, TASC and muscle morphology, TASC metabolism parameters and inflammatory parameters of the evaluated tissues. However, the effect of physical training was superior to the HP diet by protecting the trained animals from changes in the redox balance and inflammatory profile in a more pronounced way, in addition to determining the increase in the serum concentration of irisin. Conclusion: In the model studied, the effects of changes in dietary composition and physical training were decisive in protecting animals from changes caused by obesity on parameters of body composition, tissue morphology and metabolism, and the inflammatory and oxidative profile of adipose tissues. Our findings reinforce the importance of regular physical training by determining a higher concentration of circulating irisin and positive modulation in the redox balance and inflammatory profile of all tissues evaluated.

Thèses
1
  • ISRAEL SOUZA RIBEIRO
  • Brazilian green propolis and antimicrobial photodynamic therapy: characterization, in vivo evaluation and development of bioproducts for the treatment of infections caused by antibiotic-resistant bacteria

  • Leader : ROBSON AMARO AUGUSTO DA SILVA
  • MEMBRES DE LA BANQUE :
  • AMELIA CRISTINA MENDES DE MAGALHAES GUSMAO
  • GISELE LOPES DE OLIVEIRA
  • LUCAS MIRANDA MARQUES
  • LUCIANO PEREIRA ROSA
  • ROBSON AMARO AUGUSTO DA SILVA
  • Data: 22 mars 2024


  • Afficher le Résumé
  • Introduction: Skin and soft tissue infections are an important global public health problem, both due to the morbidity associated with their lesions and because they are a gateway to more invasive infections, which often culminate in the death of the affected patient. Staphylococcus aureus is the main cause of this type of infection, so its significant adaptability and the development of resistance are the main factors linked to its spread and the challenges in its treatment. In this context, antimicrobial photodynamic therapy (aPDT) with natural products has proven to be a good alternative in combating infections caused by antibiotic-resistant microorganisms, as they add benefits inherent to these compounds to the damage caused by reactive oxygen species induced by aPDT. Brazilian green propolis has known effects as an antimicrobial and immunomodulatory agent. However, it is not known for certain that such activities would be maintained if used in the context of aPDT. Objective: The objective of the present study was to characterize Brazilian green propolis as a photosensitizer for aPDT, evaluate its antimicrobial and immunomodulatory effects in vivo and develop microemulsion as a therapeutic bioproduct proposal for the treatment of intradermal infections caused by antibioticresistant bacteria. Materials and Methods: Initially, in vitro studies were carried out to characterize the antimicrobial photodynamic potential of Brazilian green propolis. To this end, UV-Vis molecular absorption spectrometry was carried out to evaluate the wavelengths with the potential to activate green propolis. Subsequently, reference strains of Methicillin-Resistant Staphylococcus aureus (MRSA ATCC 43300) and VancomycinIntermediate Staphylococcus aureus (VISA ATCC 700699) were exposed to varying concentrations of green propolis: 1µg/mL, 5µg/mL, 10µg/mL, 50µg/mL mL and 100µg/mL and stimulated by blue, green or red LED light. Next, the zeta potential of bacteria exposed to Brazilian green propolis was evaluated in order to characterize a possible site of propolis action. Soon after, high performance liquid chromatography with diode array detector coupled to tandem mass spectrometry, together with classical molecular network analysis, were performed to identify potential bioactive molecules with photodynamic activity. Finally, cytotoxicity analyzes were performed on erythrocytes and nucleated cells. After this step, the antimicrobial and immunomodulatory effects of using Brazilian green propolis as a photosensitizer against S. aureus in vivo were evaluated, in an intradermal infection model in mice. At that time, 24 Balb/c mice were infected intradermally in the ears with 1.5x108 colony-forming units of MRSA 43300. After infection, they were separated into 4 groups (6 animals per group) and treated with the vehicle, only propolis Brazilian green, only blue LED light or with aPDT protocol (Brazilian green propolis + blue LED light). Finally, microemulsion was developed as a transdermal delivery system for Brazilian green propolis, characterizing the microemulsified system and carrying out accelerated stability tests. Results: It was observed that Brazilian green propolis exhibits a pronounced absorption peak and increased photoresponsivity when exposed to blue light in the range of 400nm and 450nm. This characteristic reveals significant photodynamic activity against MRSA and VISA at concentrations from 5 µg/mL. Furthermore, propolis comprises compounds such as curcumin and other flavonoids from flavones, which have potential for photodynamic activity and other antimicrobial functions. Tests with zeta potential did not show significant differences when the bacteria were exposed to Brazilian green propolis, which suggests potential internalization of the compound by the bacteria. Furthermore, Brazilian green propolis did not present toxicity to erythrocytes and nucleated cells. In vivo, TFA with Brazilian green propolis reduced the bacterial load at the site of infection. It was also able to inhibit weight loss resulting from infection, as well as modulate the inflammatory response through greater recruitment of polymorphonuclear cells/neutrophils to the infected tissue. Finally, the microemulsion with Brazilian green propolis showed promising particle size, polydispersity index and zeta potential, in addition to having stability, verified in preliminary stability tests, with antimicrobial photodynamic activity induced by blue light being maintained. Conclusions: Brazilian green propolis presents photodynamic activity when stimulated by blue LED light, being able to induce the death of different strains of S. aureus in vitro, but also to reduce the bacterial load and modulate the inflammatory response in a murine model of intradermal infection. Furthermore, the development of a microemulsion with Brazilian green propolis shows promise, as it presents interesting physical-chemical characteristics and stability, enabling the development of protocols that do not require local injection of the photosensitizer, without generating pain and discomfort, which can reduce therapeutic abandonment.

2023
Thèses
1
  • Caroline Assunção Oliveira
  • Benefits of High-Intensity Interval Training compared to continuous training to reduce apoptotic markers in female rats with cisplatin Nephrotoxicity – possible contribution of Interleukin-11.

  • Leader : LILIANY SOUZA DE BRITO AMARAL
  • MEMBRES DE LA BANQUE :
  • LILIANY SOUZA DE BRITO AMARAL
  • RAFAEL PEREIRA DE PAULA
  • TELMA DE JESUS SOARES
  • Data: 24 mai 2023


  • Afficher le Résumé
  • Cisplatin (CP) is an antineoplastic widely used in the treatment of different types of solid tumors, but its use is mainly limited by high nephrotoxicity, which is manifested by acute kidney injury (AKI). The pathophysiology of ARF is complex and involves, among other controls, the activation of several apoptotic signal pathways. On the other hand, some studies have shown protective effects of aerobic exercise on ARF. Furthermore, mechanical stress is known to increase the production of IL-11, a pleiotropic cytokine with anti-apoptotic and anti- necrotic effects. Thus, the aim of the present study was to compare the impact of high intensity interval training (HIIT) with continuous light (LIT) and moderate intensity (MIT) training on renal IL-11 levels and expressions of apoptotic markers in tissue renal rate of CP-induced nephrotoxicity. For this purpose, 35 female Wistar rats were divided into five groups (n=7 in each group): control and sedentary (C+S); treated with CP and sedentary (CP+S); treated with CP and approved to LIT (CP+LIT); CP-treated and MIT-approved (CP+MIT) and CP-treated and HIIT-approved (CP+HIIT). Training protocols consisted of running on a motorized treadmill, 5 days a week, for 8 weeks. At the end of the 8 weeks of training, the rates received a single injection of CP (5 mg/kg) or saline solution, and 7 days after the injection they were euthanized. Serum samples and animal rinses were collected to assess serum urea urea (BUN), TNF receptor 1 (TNFR1) and 2 (TNFR2) gene expression, caspase-3, MAPK(p38) (MAPK14), p53, Bax, Bak, Bcl-2 and Bcl-xL, renal IL-11 and p53 levels, and immunolocalization of cleaved caspase-3, Bax, Bcl-2 and MAPK(p38) in renal tissue. The data reveal that all trained groups experience a significant increase in renal IL-11 levels associated with reduced local expression of pro-apoptotic markers and increased anti-apoptotic markers. Such effects were dependent on training intensity, and therefore more pronounced with HIIT. In conclusion, the present study suggests that HIIT seems to provide superior renoprotection to continuous training at mild and moderate intensities, beneficially modulating apoptotic signal pathways, and consequently attenuating ARF induced by CP in this experimental model. Furthermore, such an effect may be related, at least in part, to the increase in the renal levels of IL-11 induced by training, also dependent on its intensity.

2
  • Fernanda Karoline Almeida Freire
  • Oxidative stress markers in the context of miscarriage associated with Ureaplasma parvum infection

  • Leader : GUILHERME BARRETO CAMPOS
  • MEMBRES DE LA BANQUE :
  • CLARISSA LEAL SILVA E SOUZA
  • GUILHERME BARRETO CAMPOS
  • LILIANY SOUZA DE BRITO AMARAL
  • Data: 27 juil. 2023


  • Afficher le Résumé
  • Abortion is the termination of pregnancy before the 22nd gestational week or when the fetus weighs less than 500g. It can occur spontaneously or be induced and has multiple causes, including genital infections. Genital tract infections can ascend to the uterine cavity and account for 15% of early abortions and 66% of late abortions. The exacerbated inflammatory responses resulting from the infectious process disrupt gestational homeostasis, contributing to a pro-inflammatory profile and altering the oxidative state. The main objective of this study was to evaluate oxidative stress markers in the context of spontaneous abortion associated with infections by gynecologically significant microorganisms. Biological samples of placental tissue from women who experienced spontaneous abortion and women who had full-term deliveries were used. When evaluating oxidative stress enzymes, elevated levels of lipid peroxidation markers (TBARS and carbonylated protein) were identified in the abortion group, along with increased antioxidant activity by CAT and reduced GPx activity, while SOD showed an unchanged response. However, the profile of lipid peroxidation was accentuated in the abortion group infected with UP. GPx levels were reduced in the UP-infected abortion group compared to the infected control, while SOD and CAT showed no differences. The SOD/CAT ratio was reduced and the SOD/GPx ratio was increased in the UP groups compared to the non-infected groups. In terms of gene expression ratio, abortion contributed to an increase in Mn SOD/GPx, while UP infection reduced the expression of CuZn SOD/GPx and Mn SOD/GPx in both the abortion and infected control groups compared to the non-infected groups. Furthermore, nitrite levels were increased in the UP-infected abortion group. This study demonstrated that UP infection may contribute to altering the oxidative profile, suggesting that an imbalance in oxidative stress could contribute to the occurrence of spontaneous abortion associated with bacterial infection.

3
  • Sarah Rocha Lima Braga
  • Evaluation of anti-inflammatory, antinociceptive, and toxicological activity of the ethanolic bark extract of Commiphora leptophloeos (Mart)

  • Leader : REGIANE YATSUDA
  • MEMBRES DE LA BANQUE :
  • LUCAS MIRANDA MARQUES
  • RAFAEL SANTOS DANTAS MIRANDA DÓREA
  • REGIANE YATSUDA
  • Data: 27 juil. 2023


  • Afficher le Résumé
  • The plant species to be studied is Commiphora leptophloeos (Mart.) J.B. Gillet, popularly known as umburana fêmea of the genus Commiphora, family Burseraceae, is an endemic species of the region of the village of Palmeiras, district of the city of Contendas do Sincorá - BA. According to the local population, it is traditionally used as a tonic, healing wounds and against coughs, bronchitis, gastritis, ulcers and chronic conditions. The study aimed to evaluate the medicinal potential of this plant as an antiinflammatory, antinociceptive, antioxidant and toxicological action. The ethanolic extract was prepared by maceration and after evaporation the crude extract was obtained with a yield of 2.2%. The phytochemical prospection was carried out by CCD with specific developers and the chromatographic profile evaluated by GC-MS, highlighting the identification of: stigmasterol, lupeol, protocatechuic acid, lanosterol, ethyl oleate and ethyl linoleate. The antioxidant assay was carried out by evaluating the total antioxidant capacity, using the phosphomolybdate method, in which the plant extract showed antioxidant capacity. For nociception and inflammation assays, adult male Balb/c mice were used. The antinociceptive effect was evaluated by the tests: Abdominal writhing induced by 0.6% acetic acid, where all concentrations (25, 50, 100 and 200 mg/kg) promoted a significant reduction in nociceptive responses (p < 0.05). The concentration of 100mg/kg of the ethanolic extract demonstrated that its antinociceptive effects were mediated by the cholinergic pathway (p < 0.05). Intraplantar injection of 1.5% formalin, in phase 1 and 2, all concentrations (50, 100 and 200 mg/kg) reduced the number of flinches, compared to the negative control (p < 0.05), when incidents to the morphine positive control group, the concentrations of 50 and 200 mg/kg did not show statistical difference (p < 0.05), the paw edema formed did not obtain a significant reduction in any experimental concentration (p < 0.05). In electronic Von Frey by intraplantar injection of carrageenan (Cg), all concentrations (50, 100, 200 mg/kg) were able to significantly reduce hypernociception (p < 0.05). For the experiment of anti-inflammatory activity, tests were performed: Migration of neutrophils to the peritoneal cavity, where all concentrations (50, 100, 200 mg/kg) established a significant reduction in neutrophil migration in (p < 0.05) ; The determination of nitrite levels, all concentrations (50, 100, 200 mg/kg) showed a significant reduction (p < 0.05). Evaluation of vascular permeability by Evans blue, which showed a significant reduction in dye leakage into the peritoneal fluid at all doses (50, 100, 200 mg/kg), (p < 0.05). Toxicity innovation was performed with Artemia salina Leach and the toxicity classification was highly toxic. Cytotoxicity was investigated using the MTT assay, where concentrations of 25, 50 and 100ug/kg were shown to decrease tumor cell viability (p < 0.05). The results allow us to consider that C. leptophloeos (Mart.) is a promising natural source for the identification of new bioactive compounds and therapeutic agents, as well as a promising species for use as a herbal medicine

4
  • Anne Caroline Brito Barroso
  • Cytokine signature profile in the genital tract of adolescent men who have sex with men (MSM) associated with sexually transmitted infections (STIs).

  • Leader : GUILHERME BARRETO CAMPOS
  • MEMBRES DE LA BANQUE :
  • ALINE TEIXEIRA AMORIM
  • GUILHERME BARRETO CAMPOS
  • LUCAS MIRANDA MARQUES
  • Data: 1 août 2023


  • Afficher le Résumé
  • Sexually Transmitted Infections (STIs) are defined as a group of diseases caused by microorganisms transmitted mainly through sexual contact without the use of condoms. In addition to HIV, other bacterial STIs are considered epidemic in Brazil, especially gonorrhea (Neisseria gonorrhoeae), mycoplasma infections (Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum, Ureaplasma parvum) and Chlamydia trachomatis. During STI infection, immune cells produce a series of chemical mediators such as: tumor necrosis factor alpha (TNF-α), interleukins IL1-β, IL-6, IL-10, among others, which act by orchestrating the immune response. Objective: to define the signature of in young men who have sex with men and transsexual women, correlating the results with the prevalence of STIs due to Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasmas. Methodology: This is a cross-sectional study that is part of a pilot project entitled “PrEP Study 15-19” (Title: Study of the effectiveness of Pre-Exposure Prophylaxis [PrEP]. Clinical samples were collected in duplicate from each participant , at the time of the first visit to the service. For this, they were obtained by rubbing a swab on the penile, oral and anal urethral mucosa, being stored in 5 mL of transport medium. The quantification of microorganisms was performed using the absolute quantification technique IL-1β, IL-6, IL-10 and TNF-α tumor necrosis factor assays were performed using an eBioscience ELISA kit. Results: Our sample consisted predominantly of black men who have sex with men or brown, aged between 18 and 19 years. Of these, 17.36% had one or more infections. There was an association between complete high school education and STI (p 0.045). Among the studied STIs, the prevalence of 85.3% stands out of mycoplasmas.In the evaluation of the profile of cytokines secreted between infected and non-infected, we found no statistically significant association. Matrix tests were performed among those infected with an association between higher TNF-α and IL-6 values. In the non-infected population, there is a general association between cytokines, that is, participants with lower levels showed a reduction in all cytokines studied. In this study, we had a prevalence of 4.73% of coinfections, all with at least one mycoplasma. 50% of the coinfections found were Mycoplasma hominis and Ureaplasma urealyticum. In the evaluation of the cytokine signature between mono- and co-infected individuals, we found higher levels of IL-1β in monoinfected individuals when compared to co-infected individuals and of TNF-α in monoinfected individuals, when compared to non-infected and co-infected individuals. In observing the heatmap with unsupervised clusters, two groups can be seen, one with a greater inflammatory potential, and the other with a lower potential, with emphasis on M. hominis and U. urealyticum with a high potential for an inflammatory response. The Principal Component Analysis shows the association between M. hominis infection and IL1-β secretion. Conclusion: Our study found no statistical difference between infected and uninfected young people, however, mycoplasma infection and co-infection with gonorrhea and chlamydia demonstrate an association with increased cytokines.

5
  • Everton Almeida Sousa
  • Effects of therapeutic or preventive training on function, morphology and redox balance in brown adipose tissue in an animal model of aging and obesity 

  • Leader : AMELIA CRISTINA MENDES DE MAGALHAES GUSMAO
  • MEMBRES DE LA BANQUE :
  • AMELIA CRISTINA MENDES DE MAGALHAES GUSMAO
  • Luciano Evangelista dos Santos Filho
  • TELMA DE JESUS SOARES
  • Data: 11 août 2023


  • Afficher le Résumé
  • Objective: To evaluate the effects of therapeutic or preventive physical training on morphological and functional parameters in brown adipose tissue in an animal model of aging and obesity. Methods: Twenty-four male Wistar rats (initial age = 4 months and final age = 14 months) were randomly distributed into three elderly and obese experimental groups (n= 8/group): sedentary (EOS), therapeutic exercise (EOT) and preventive exercise (EOP). Body adiposity parameters were evaluated and, in brown adipose tissue (BAT), the activity of antioxidant enzymes, TBARS and total nitrites, morphology parameters, and gene expression of redox profile markers and tissue function. Results: Preventive exercise reduced the mass of abdominal subcutaneous adipose tissue in aged and obese animals. Total visceral abdominal adipose tissue (TAV) weight reduces in the EOT and EOP exercised groups. In the TAM, the exercise protocols, therapeutic and preventive, determined the increase in the number of adipocytes per field, reduction in the number of unilocular adipocytes, and increase in the number of multilocular adipocytes. The TAM's percentage of lipid vacuoles per field was reduced only in the EOP group. TBARS and total nitrite levels were reduced by therapeutic and preventive exercise protocols, with the reduction being more remarkable in the EOP group. The activity of the antioxidant enzyme catalase was higher in animals from the EOT and EOP groups. The activity of the GPx enzyme increased only in the preventively trained animals, although the immunostaining for GPx was higher in both the EOT and EOP groups. The analysis of the expression of the genes that encode the enzymes Catalase, GPx-1, and SOD-1 in brown adipose tissue revealed that both therapeutic and preventive exercise increased the gene expression of the antioxidant enzymes, Catalase and GPx-1, with a more significant effect of preventive training. No differences were observed between groups in SOD-1 enzyme gene expression. The gene encoding the UCP-1 protein expression in brown adipose tissue increased in the EOP and EOT groups, while the expressions of PGC-1a and SIRT 1 increased only in the EOP. Conclusion: The therapeutic and preventive exercise protocols determined improved morphology, function, and oxidative stress parameters in the brown adipose tissue of aged rats with diet-induced obesity. The preventive protocol's beneficial effects were more evident, indicating the role of regular exercise practice in attenuating or reversing alterations in brown adipose tissue in the studied animal model.

6
  • TAYLAN CUNHA MEIRA
  • Impact of physical training on changes in the oxidative profile and cardiovascular morphofunctional parameters in an animal model of obesity induced by a hypercaloric diet.

  • Leader : AMELIA CRISTINA MENDES DE MAGALHAES GUSMAO
  • MEMBRES DE LA BANQUE :
  • AMELIA CRISTINA MENDES DE MAGALHAES GUSMAO
  • ROBSON AMARO AUGUSTO DA SILVA
  • GRAZIELLE PRATES LOURENCO DOS SANTOS BITTENCOURT
  • Data: 13 déc. 2023


  • Afficher le Résumé
  • Introduction: Obesity is characterized as a chronic and complex condition that contributes to negative impacts on human health. In its genesis, genetic, environmental, metabolic and behavioral factors act that can determine a reduction in quality of life, predisposing the population to metabolic and cardiovascular diseases. Faced with this problem, physical exercise is an important strategy for reducing body adiposity and preventing cardiovascular disorders associated with obesity. Objective: To evaluate the impact of physical exercise on changes in the oxidative profile and cardiovascular morphofunctional parameters in an animal model of obesity induced by a high-calorie diet. Methods: We used 24 male Wistar rats weighing between 150 and 200g, whose study protocol was approved by the Ethics Committee on the Use of Animals (CEUA/IMS-UFBA) under opinion number 053/2017. Initially, the experimental animals were subjected to a normocaloric control diet (DC, n=10) or a hypercaloric diet (DH, n=14) to induce obesity for 8 weeks. After this period, the animals in the control diet group (CD) or the hypercaloric diet group (HD) were subdivided into 2 experimental groups each, which were trained on a motorized treadmill (DCT, n=5; DHT, n=7) or maintained sedentary (DCS, n=5; DHS, n=7) for 12 weeks. At the end of the experiment, the abdominal adipose tissue deposits were dissected and weighed and the ventricle and aorta were removed for histological analysis. Chest blood was collected for biochemical and hormonal analysis. The histological sections were stained with Hematoxylin-Eosin (HE) and Masson's Tricromion (TM) and analyzed by the computerized system (ImageJ). Results: Consumption of a high-calorie diet resulted in an increase in food and caloric intake, body weight and adiposity, and altered glucose tolerance. The training protocol applied reduced the body weight, adiposity index, and abdominal adipose tissue of animals submitted to the high-calorie diet. No significant changes were observed in fasting blood glucose, insulin, HOMA-IR, HOMA-b, and Quick. Systolic blood pressure increased in sedentary animals that consumed the high-calorie diet and was reduced by the physical training protocol by approximately 12%. CK/MB levels were reduced in trained animals compared to sedentary animals subjected to a high-calorie diet. Animals submitted to a high-calorie diet had larger areas in the thickness of the aortic tunica intima, consequently, these animals had smaller aortic lumens; while trained animals had smaller thicknesses and larger lumens. The areas of cardiomyocytes and capillarization demonstrated pathological cardiac adaptations in sedentary animals that consumed a high-calorie diet, while in trained animals’ were noted increased cardiomyocyte area and new vascularization in both diets. Sedentary animals submitted to a high-calorie diet showed larger areas with fibrosis, while the training protocol reduced these areas. The training applied in this study increased catalase and GPX values; while lipid peroxidation values (TBARS) had lower rates in trained animals. Cardiac total nitrite levels were higher in the (DHS) group and in the trained groups regardless of diet. Conclusion: The training protocol determined an improvement in body adiposity, oxidative profile and cardiovascular morphofunctional parameters in the animal model of diet-induced obesity.

     

     

Thèses
1
  • Igor Pereira Ribeiro Muniz
  • Antimicrobial photodynamic therapy (aPDT) with curcumin controls intradermal infection by resistant 
    Staphylococcus aureus methicillin in mice with type 1 diabetes
  • Leader : ROBSON AMARO AUGUSTO DA SILVA
  • MEMBRES DE LA BANQUE :
  • AMELIA CRISTINA MENDES DE MAGALHAES GUSMAO
  • DENISAR PALMITO DOS SANTOS
  • LUCIANO PEREIRA ROSA
  • ROBSON AMARO AUGUSTO DA SILVA
  • TELMA DE JESUS SOARES
  • Data: 28 avr. 2023


  • Afficher le Résumé
  • Type 1 Diabetes Mellitus (T1DM) is a chronic non-communicable disease in which insulin is insufficiently produced due to the destruction of β cells in the pancreas. The changes generated by this condition increase the risk of infections for these individuals. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the main pathogens causing infections in individuals with diabetes. In this work, we aimed to investigate the effects of the application of photodynamic therapy (PDT), using curcumin as a photosensitizer (PS), in the treatment of intradermal infection in mice with T1DM. C57bl/6 mice were weighed and, in a fasting state, their blood glucose was measured. DMT1 was induced by intraperitoneal injection of a single dose of streptozotocin (STZ) (180 mg/kg). Five days after STZ administration, the animals' blood glucose was measured to confirm the establishment of DMT1. Fifteen days after DMT1 induction, the animals were weighed and then infected intradermally in the left ear. For infection, the concentration of 1.5 x 107 CFU of the MRSA ATCC 4330 strain was quantified. Twentyfour hours after infection, experimental treatments were performed. A solution containing 100 μg of curcumin was photoactivated ex vivo using LED light (450 nm) obtaining a fluence of 13.5 J/cm2 . After photoactivation, the solution was inoculated at the same site where the infection was carried out. Control treatments consisted of the application of non-photoactivated PS or sterile saline. The animals were euthanized 24 h after the treatments and the left ear and left retromaxillary lymph node were surgically collected. The lymph node was macerated in saline for analysis of bacterial load, measurement of cytokines by ELISA, measurement of nitrites and nitrates, and cell counts. The ear was used to make slides that were stained by H&E or stained with anti-myeloperoxidase (MPO) antibodies by immunohistochemistry. Slides were photomicrographed and cell counts and tissue MPO expression analyzes were performed. The PDT group had a lower bacterial load in the lymph node when compared to controls (p-value <0.05). In addition to the lower bacterial load, the PDT group also had higher levels of nitrates and nitrites in the lymph node when compared to controls (p-value >< 0.001). Cell recruitment to the infectious site was similar between the groups, however, the expression of MPO in the PDT group was less intense compared to the saline group (p-value < 0.001). When analyzing the production of cytokines, the PDT group showed lower production of IL-1, IL-12, and IL-10 (p-value <0.01; p-value ><0.05; p-value >< 0.05, respectively), when compared to the saline group. This study shows, for the first time, the therapeutic potential of PDT using curcumin in the treatment of an intradermal infection caused by S. aureus in mice with T1DM.

2
  • Thiago Macêdo Lopes Correia
  • IN VIVO AND IN VITRO STUDIES OF THE EFFECTS OF PHYSICAL TRAINING ON MUSCLE CHANGES RESULTING FROM THE ASSOCIATION BETWEEN OBESITY AND AGING. 

  • Leader : AMELIA CRISTINA MENDES DE MAGALHAES GUSMAO
  • MEMBRES DE LA BANQUE :
  • AMELIA CRISTINA MENDES DE MAGALHAES GUSMAO
  • ROBSON AMARO AUGUSTO DA SILVA
  • LUCAS MIRANDA MARQUES
  • LEANDRO MARTINS DE FREITAS
  • ANDREA PIRES DOS SANTOS
  • Data: 8 déc. 2023


  • Afficher le Résumé
  • Objective: To investigate the effects of aerobic physical training performed therapeutically or throughout life on histological changes, redox balance, inflammation, and metabolism in skeletal muscle and cardiac ventricle caused by the association between aging and obesity in vivo and in vitro.

    Methods: The experiment was divided into a pilot study and a main study. The pilot study aimed to identify the age at which changes in muscle and physical performance begin in response to natural aging. Thus, 41 male Wistar rats aged 4 months were randomly distributed into 6 groups defined by age at euthanasia, these being 4 (n = 5), 8 (n = 5), 12 (n = 7), 14 (n = 8), 18 (n = 8) and 20 months (n = 8). Throughout the experimental protocol, the animals were weighed weekly, and physical performance was assessed monthly using the maximal running test on a motorized treadmill for rats. After defining the age at which muscle decline began (14 months), the influence of physical training on the changes observed was evaluated. To this end, 32 4-month-old male Wistar rats were randomly distributed into two groups: sedentary group (n = 16) and trained group (n = 16). Upon reaching 8 months of age, 8 animals from each group were euthanized, forming the young sedentary and trained groups. The remaining animals continued until they reached 14 months of age, and constituted the sedentary and trained aged groups. Training was carried out on a motorized treadmill for rats, at moderate intensity, on alternate days and lasting 1 hour per session. The animals were euthanized 24 hours after the last training session. Blood, adipose tissue and muscle samples were collected, duly measured and stored in an ultra-freezer -80 °C, or fixed. The frozen samples were used to quantify the inflammatory and oxidative profiles, and the samples were fixed for histological studies. The main study consisted of an in vivo and an in vitro study. The in vivo protocol was carried out with 32 male Wistar rats that were randomly distributed into four groups (n = 8/group): aged sedentary group (ESed), aging sedentary group fed a high-fat diet (HFD) (ASed+HFD), aging trained therapeutically and fed with HFD (ATT+HFD) and aging lifelong trained and fed with HFD (ALT+DHL). 24 hours after the last physical training session, all animals were euthanized and then the gastrocnemius muscle and cardiac ventricle were collected for histological, immunohistochemical, redox balance, inflammation and metabolism studies. The gastrocnemius muscle was used to analyze mRNA and microRNA expression by qPCR. Abdominal adipose tissue deposits were collected and weighed to determine body composition. For in vitro studies, primary macrophages obtained from the peritoneal exudate of 6 4-month-old male BALB/c mice, elicited through the administration of thioglycolate (3%), and primary myoblasts isolated from the gastrocnemius muscle of a 4 month old male rat were used. Cultures of macrophages and myoblasts were exposed to serum from the animals from the in vivo study for 24h. The cultures were used to analyze cell viability by MTT, total nitrites and hydrogen peroxide and to analyze the expression of genes involved in the inflammatory response and muscle metabolism. All variables of interest in this study were subjected to the Shapiro-Wilk normality test. Comparisons between pilot test groups were made using the ANOVA test for repeated measures (temporal analysis) and one-way ANOVA, followed by the Tukey post-test. For analyzes between young and aged, sedentary and trained groups, a factorial design (2x2) was adopted using the two-way ANOVA test. Analyzes of in vivo and in vitro studies were performed using Student's T test and one-way ANOVA test.

    Results: The results of the pilot study indicate that the decline in muscle function begins at 14 months of age, evidenced by the reduction in physical performance, lean mass and gastrocnemius muscle weight and antioxidant capacity of the muscle. On the other hand, the physical training routine up to 14 months improved body composition, inflammatory profile, redox status and protected the muscle against reduction in the cross-sectional area of the fibers. The in vivo study showed an unfavorable outcome in response to the association between aging and diet-induced obesity on muscle and cardiac parameters, morphology, fibrosis, inflammation, oxidative stress and metabolism. Furthermore, an increase in the expression of miRNA-21 and genes involved in the pro-inflammatory and catabolic response, and a reduction in the expression of genes involved in the antioxidant and anabolic response were observed in the gastrocnemius muscle. Physical training, especially the lifelong training protocol, attenuated the findings resulting from the association between aging and obesity on muscular and cardiac parameters, reduced the expression of miR-21 and increased the expression of miR-486. In in vitro studies, macrophages and myoblasts exposed to serum from aging and obese animals showed an increase in the pro-inflammatory and catabolic profile, respectively, while serum from trained animals, especially those that had undergone lifelong training, determined reduction of the pro-inflammatory and catabolic profile of cell cultures.

    Conclusion: In the animal model studied, the association between sedentary lifestyle, aging and obesity induced by a high-fat diet determined muscle damage, especially in the inflammatory, oxidative and metabolic profiles, and these changes appear to be associated with the positive modulation of miR-21. On the other hand, regular physical exercise, especially throughout life, attenuated the changes caused by the association between aging and obesity in all parameters studied, in vivo and in vitro. Our findings reinforce the importance of adopting exercise routines throughout life as an effective tool against the effects of age, especially when associated with unhealthy eating habits.

2022
Thèses
1
  • Gabriela Freitas Silva Bitencourt
  • Impact of physical exercise on inflammatory and apoptotic changes and redox status in rats with type 1 diabetes mellitus.

  • Leader : TELMA DE JESUS SOARES
  • MEMBRES DE LA BANQUE :
  • LILIANY SOUZA DE BRITO AMARAL
  • SAMIRA ITANA DE SOUZA
  • TELMA DE JESUS SOARES
  • Data: 15 juil. 2022


  • Afficher le Résumé
  • Diabetic nephropathy is often associated with increased oxidative stress by the generation of reactive oxygen species (ROS), which can provoke a sequence of pro-inflammatory, pro-apototic responses and endothelial dysfunction in the kidneys. New therapeutic strategies are needed to attenuate and/or prevent the progression of diabetic nephropathy. Therefore, this study evaluated the impact of two exercise protocols on oxidative, inflammatory and apoptotic changes induced by type 1 diabetes mellitus (DM1) in the renal tissue of female rats. For this, 30 female Wistar rats were used and divided into 5 groups: SC - sedentary control rats (n=6), TC - trained control rats (n=6), SD - sedentary diabetic rats (n=6), TD - rats trained diabetic rats (n=6) and PTD – previously trained diabetic rats (n=6). Only the PTD group was submitted to four weeks of exercise before the induction of diabetes. Then, DM1 was induced in the SD, TD and PTD groups with streptozotocin (40mg/kg, iv), and the PTD and TD groups underwent 8 weeks of exercise. The TC group also was submitted 8 weeks of exercise after administration of citrate (0.1 M, iv). Kidney tissue was removed for oxidative stress, immunohistochemistry, ELISA and Western blot studies. Our data show that exercise training reduced TBARS levels and increased superoxide dismutase activity in the renal tissue of rats of the TD and PTD groups. However, only previous exercise increased the activity of the enzyme glutathione peroxidase in the PTD group. Furthermore, exercise reduced the expression of caspase-3, p-p38 and M1 macrophages and increased M2 macrophages and Bcl-2, as well as IL-10 levels in kidney tissue of the TD and PTD groups. Only exercise initiated before diabetes induction reduced TNF-alpha levels in the DPT group. In conclusion, our data demonstrate that moderate intensity aerobic exercise improved redox status, inflammation and apoptosis. However, exercise initiated prior to the induction of diabetes promoted additional effects by increasing glutathione peroxidase activity and reducing TNF-alpha levels in the kidney tissue of female Wistar rats.

2
  • Paulo Henrique Bispo Lima
  • Postmenopausal diabetes and hypertension: interactions between severity and failure to control inflammation
  • Leader : ROBSON AMARO AUGUSTO DA SILVA
  • MEMBRES DE LA BANQUE :
  • DIRCEU JOAQUIM COSTA
  • ROBSON AMARO AUGUSTO DA SILVA
  • TELMA DE JESUS SOARES
  • Data: 9 déc. 2022


  • Afficher le Résumé
  • INTRODUCTION/OBJECTIVE: Aging in women is associated with changes resulting from the climacteric, which culminates in changes in body composition, metabolic and hormonal changes, which are more susceptible to the development of chronic non-communicable diseases (NCDs). Among the chronic diseases with the highest incidence in this population, diabetes mellitus (DM) and systemic arterial hypertension (SAH) stand out. These diseases, despite the different organs and systems involved, have a common risk factor: in general, clinically silent low-grade inflammation that contributes to the pathogenesis and progression of age-related diseases. Therefore, this work aimed to carry out an expanded study on the interactions of anthropometric, biochemical and inflammatory parameters associated with the risk of the severity of these diseases in elderly postmenopausal women. METHODS: The study involved the evaluation of 126 elderly women with a positive diagnosis of arterial hypertension and diabetes mellitus. The groups were divided into risks proposed by the European Society of Cardiology. Anthropometric data were collected with bioimpedance analysis, while inflammatory and biochemical data were obtained from blood collection. The sera obtained were evaluated by enzymatic assays. Statistical analyzes were performed using GraphPad Prism, and correlations were analyzed using R Studio software. RESULTS: Waist circumference and waist circumference/height ratio were higher in the very severe risk group when compared to the mild risk group. Lean body mass (p< 0.011) decreases with increasing risk of severity. Systolic (p< 0.0002) and diastolic (p< 0.0054) pressures increased in parallel with the increase in severity in relation to groups. Biochemical markers increased with the risk of severity: glucose, triglycerides, cholesterol, LDLc and VLDLc, except HDLc. Regarding the inflammatory data, it was possible to observe that the inflammatory cytokines IL-1β, IFN-γ, TNF-α increased together with the severity. However, the anti-inflammatory cytokine IL10 (p=0.0293) decreased in the very severe risk group. Cytokine ratios showed different patterns between groups. The group of elderly women at very severe 9 risk had lower values for the ratios IL-10/IL-1β (p< 0.05), IL-10/IL-17 (p< 0.05) and IL-10/TNF- ɑ (p< 0.01) when compared with elderly women at severe risk. The patterns of correlations for biochemical, inflammatory and body composition variables are different between groups. However, the very severe risk group observes lower correlation forces for some parameters and the emergence of other interactions. CONCLUSION: The results showed to be extensively altered in the very severe risk group, where the inflammatory profile loses its responsiveness as the severity increases. This is the first work that shows an expanded view of the complex interaction between the different parameters evaluated in elderly hypertensive and diabetic women.

3
  • CAMILA DUTRA BARBOSA
  • Evaluation of the role of serotonin in the response of macrophages obtained from mice inoculated with Staphylococcus aureus and Escherichia coli

  • Leader : LUCAS MIRANDA MARQUES
  • MEMBRES DE LA BANQUE :
  • FABRICIO FREIRE DE MELO
  • LUCAS MIRANDA MARQUES
  • TELMA DE JESUS SOARES
  • Data: 16 déc. 2022


  • Afficher le Résumé
  • Serotonin (5-hydroxytryptamine or 5-HT) modulates immune responses in immune cells, and this action occurs through the serotonin system. This monoaminergic neurotransmitter acts on immune cells, coordinating the immune responses of macrophages, Natural killer (NK) cells, dendritic cells, and lymphocytes, either inhibiting or stimulating them. This immunomodulatory role occurs mainly in cells with pro-inflammatory action, especially the effects of 5-HT on different immunological stimuli in specific tissues that are not known. Thus, the present study aimed to evaluate the effect of 5-HT on the immune response induced by inoculation of Staphylococcus aureus and Escherichia coli in the culture of peritoneal and splenic macrophages from mice treated or not with serotonin. For this, mice of the C57BL6 strain were used. The first animal was treated with 5-HT in vivo, where the ventricular group mice were operated on by intracerebral surgery (ICV). The second group of sham animals experienced an ICV surgery; however, only 0.1% ascorbic acid (vehicle) was administered. After surgery, peritoneal and splenic macrophages were extracted from the animals and incubated for 24 hours. The sham group was divided into two subgroups: macrophages treated with 5-HT in vitro and untreated macrophages. The macrophages treated in vitro received different doses of 5-HT (10-3 M and 10-8 M) and were again incubated for 24 hours, while the subgroup of untreated macrophages did not undergo any contact with 5-HT. After the incubation period, respectively, negative macrophages treated in vivo, in vitro, and untreated were infected with E. coli and S. aureus, LPS (positive control), or saline (control) and incubated again for 3 hours. After collection, the gene expression of the cytokines TNF-α, IL1β, and IL-6 was performed in the cells, as well as the reactive oxygen and nitric oxide species in the supernatant. In general, macrophages from animals treated in vivo with 5-HT and macrophages treated in vitro with 10-3 M and 10-6 M 5-HT showed lower inflamed marker faces when compared to macrophages without any treatment, mainly for infections using E. coli and S. aureus. The same effect was not observed with in vitro treatment using 10-8 M 5-HT. In addition, serotonin may also be used in the future as a therapeutic agent in the treatment of inflammatory diseases. However, studies are carried out for more studies carried out in this process.

Thèses
1
  • GRAZIELLE PRATES LOURENCO DOS SANTOS BITTENCOURT
  • Effects of high-fat diets with coconut or linseed oil carbohydrate-restricted and exercise on metabolic and hepatic parameters in obese rats.

  • Leader : AMELIA CRISTINA MENDES DE MAGALHAES GUSMAO
  • MEMBRES DE LA BANQUE :
  • AMELIA CRISTINA MENDES DE MAGALHAES GUSMAO
  • ROBSON AMARO AUGUSTO DA SILVA
  • MATHEUS LOPES CORTES
  • RAILDO DA SILVA COQUEIRO
  • RAFAEL PEREIRA DE PAULA
  • Data: 1 août 2022


  • Afficher le Résumé
  • Objective: To evaluate the effects of high-fat diets with coconut or linseed oil carbohydrate-restricted and moderate-intensity exercise on metabolic and hepatic parameters in obese rats. Methods: Fifty-four male Wistar rats were used and initially received a control (n=6) or hypercaloric (n=48) diet for 8 weeks to induce obesity. After this period, the animals of the control group (n=6) and part of the hypercaloric group (n=6) were euthanized and the others were subdivided into six groups, with different diets and submitted or not to moderate-intensity physical exercise for 12 weeks: hypercaloric and sedentary (n=7); hypercaloric and exercised (n=7); high-fat diet with coconut oil carbohydrate-restricted and sedentary (n=7); high-fat diet with coconut oil carbohydrate-restricted and exercised (n=7), high-fat diet with linseed oil
    carbohydrate-restricted and sedentary (n=7) and high-fat diet with linseed oil carbohydrate-restricted and exercised (n=7). Dietary, cardiovascular, and body composition parameters were evaluated, as well as lipid and plasma inflammatory profile, glycemic homeostasis, insulin resistance and sensitivity. In addition, the development of steatosis, inflammation, fibrosis, and oxidative stress in liver were evaluated. Results: The experimental model of diet-induced obesity was validated. The high-fat diet with coconut oil carbohydrate-restricted reduced food and caloric intake, but increased body adiposity, blood pressure, glucose and insulin levels, reduced IL-10 levels, increased liver cholesterol, promoted macrovesicular fat deposition, inflammation, fibrosis and oxidative stress in liver tissue. The high-fat diet with linseed oil carbohydrate-restricted, although it increased caloric intake, did not increase body mass and adiposity, improved lipid profile, reduced IL6 and IL-10 levels, oxidative stress and the deposition of macro and microvesicles of fat in the liver, however, promoted hepatic inflammation and hyperglycemia. Exercise enabled beneficial effects on most of the metabolic and hepatic parameters analyzed. Conclusion: Consumption of the high-fat diet with coconut oil carbohydrate-restricted
    negatively impacted body adiposity and systemic and hepatic metabolic and inflammatory profiles, while consumption of the high-fat diet with linseed oil carbohydrate-restricted and exercise had beneficial effects on most of the metabolic and hepatic parameters analyzed. Thus, caution is suggested in the use of these diets, even when associated with exercise, reinforcing the need for further studies to determine safety recommendations for including these oils in the diet.

2
  • LAÍS FERRAZ BRITO SOUSA
  • Evaluation of the biological activities of the association of β-caryophyllene and docosahexaenoic acid in experimental models in vitro and in vivo.

  • Leader : LUCAS MIRANDA MARQUES
  • MEMBRES DE LA BANQUE :
  • DAIANA SILVA LOPES
  • FABRICIO FREIRE DE MELO
  • HELLEN BRAGA MARTINS OLIVEIRA
  • LUCAS MIRANDA MARQUES
  • REGIANE YATSUDA
  • Data: 12 août 2022


  • Afficher le Résumé
  • Introduction: Inflammation is a complex biological response involving the immune, autonomic, vascular and somatosensory systems, which involves the synthesis of inflammatory mediators and pain induction by activating nociceptors. One of the most common and impacting causes of inflammation in public health is infection by Staphylococcus aureus, the main cause of bacteremia, with worse in-hospital clinical outcomes. Antioxidant substances have been evaluated in this context as an analgesic, antioxidant, anti-inflammatory, antitumor, and bactericidal therapeutic alternatives. Among them, the essential oils of aromatic plants, such as β-caryophyllene (BCP), and polyunsaturated fatty acids, such as Docosahexaenoic acid (DHA) stand out. Objective: To evaluate the biological activities of the BCP-DHA association in vitro and in vivo experimental models of antinociception and inflammation. Materials and methods: For that, the antinociceptive effects were evaluated in animal models through tests of abdominal writhing induced by acetic acid, paw edema induced by intraplantar injection of formalin, and VonFrey hypernociception. To determine the anti-inflammatory effects, monocytes isolated from peripheral blood of adult male volunteers were infected with methicillin-resistant Staphylococcus aureus and incubated with treatment for subsequent cytokine measurement and gene expression analysis. The antioxidant capacity was evaluated by the DPPH method. The MTT assay was performed to determine the cell viability of the A549 and BEAS lung lines against treatment with BCP-DHA and then, adhesion and migration tests were performed with the doses of the associations determined in the previous test. Results: Antinociceptive effects were observed in the three models performed when comparing the control (saline) and BCP-DHA treated groups, obtaining statistical significance (p < 0.05) in the test of abdominal writhing induced by acetic acid, in the evaluation of flinches and Paw licking in the intraplantar formalin injection model and in Von Frey test hypernociception. There was a significant reduction in the levels of GM-CSF, TNFα, IL-1, IL-6, and IL-12, as well as an increase in IL-10 in the groups submitted to treatment with the BCP-DHA association, as well as negative regulation of the expression of genes involved in the intracellular inflammatory signaling cascade (IL-2, IL-6, IRF7, NLRP3, and TYK2) in all groups that received treatment, regardless of the presence of infection. In the DPPH test, only BCP showed significant scavenging of free radicals, with EC 50 = 2.82 ± 0.06 M. There was the significant cytotoxic activity of the 2 combinations of BCP-DHA tested on the A549 tumor cell line, as well as important inhibition of cell adhesion and migration. There was underexpression of genes involved in the cell cycle, DNA repair, nucleotide excision, mismatched bases and post replication, and maintenance of telomeres, oncogenes, and tumor suppressors. Therefore, our results strongly suggest that the association of BCP-DHA emerges as a possible new therapeutic alternative with analgesic, anti-inflammatory, antiangiogenic, pro-apoptotic, and antiproliferative effects.

3
  • DÉBORAH CRUZ DOS SANTOS
  • Influence of 5α-dihydrotestosterone on the response of murine peritoneal macrophages and human monocytes induced by Staphylococcus aureus

  • Leader : LUCAS MIRANDA MARQUES
  • MEMBRES DE LA BANQUE :
  • CLARISSA LEAL SILVA E SOUZA
  • GUILHERME BARRETO CAMPOS
  • HELLEN BRAGA MARTINS OLIVEIRA
  • LUCAS MIRANDA MARQUES
  • TELMA DE JESUS SOARES
  • Data: 15 sept. 2022


  • Afficher le Résumé
  • Introduction: Staphylococcus aureus infections have a high morbidity and mortality rate, considered a major problem for public health. There is little information about the role of dihydrotestosterone in infections caused by S. aureus. Objective: To evaluate the influence of 5α-dihydrotestosterone (DHT) on the response of murine peritoneal macrophages (MPMs) and human peripheral blood monocytes (hPMs) in the immune response induced by Staphylococcus aureus. Methodology: An in vitro model was performed from male orchiectomized (OQX) and female BALB/C Shams MPMs and from healthy young male and female MPMs of childbearing age, with sex steroid levels within the normal range. Cells were inoculated with 10μl of S. aureus cap 80 or with sterile saline (control) for a period of 6h. Cells from OQX males, females, male and female hPMs were also pre-treated with a concentration of 100μl (10-2M) of DHT for 24h before stimulation with S. aureus. Cytokines TNF-α, IL-1α, IL-1β, IL-6, IL-8, IL-12, IL-10, GM-CSF, total nitrites, hydrogen peroxide (H2O2) were measured in culture supernatant. in MPMs and in hPMs. In addition, 84 genes involved in the immune response against S. aureus were analyzed by RT-PCR array. Results: In MPMs, cells inoculated with S. aureus from Sham males showed higher levels of inflammatory cytokines and lower concentrations of IL-10, total nitrites and H2O2 compared to OQX. Cells from male Sham inoculated with S. aureus also showed higher concentrations of pro-inflammatory cytokines and lower concentrations of IL-10, total nitrites and H2O2 compared to females. In the treatment with DHT, the concentration of inflammatory cytokines and the expression of genes such as TLR-2 and genes involved in the NF-kB pathway were higher in OQX treated with the hormone compared to OQX without pretreatment. In addition, the concentrations of total nitrites and H2O2 were lower in pre-treatment cells, both in OQX male and female cells. For the human experiment, all selected research subjects were healthy and sex hormone levels were within the normal range for men and women of childbearing age (17β-estradiol, progesterone, follicle-stimulating hormones (FSH), luteinizing hormones ( LH) and testosterone). hPMs inoculated with S. aureus from men had higher concentrations of inflammatory cytokines and lower concentrations of IL-10, lower levels of total nitrites and H2O2 compared to women. In response to treatment, with DHT, the hormone inhibited the concentrations of total nitrites and H2O2 in both men and women, and we observed greater expression of TLR-2 and genes involved in the NF-kB pathway, similar to the results in mice. Conclusion: Our results showed that there is a difference between the sexes in the response to inoculation by S. aureus and that DHT has pro-inflammatory immunomodulatory properties in MPMs and in hPMs. The hormone stimulated greater release of inflammatory cytokines, genes involved in this response, and suppressed the release of important inflammatory markers for phagocytosis against S. aureus. Regarding sex, females performed a better immune defense response against this pathogen. This work presents an approach not presented in the literature, with data on the role of DHT in the inflammatory response against S. aureus, which can be considered important results to generate new studies in androgens and their role in the response against microorganisms, which is of great scientific interest.

4
  • FERNANDA DE ABREU SILVA
  • Study of the mechanisms involved in the beneficial effects of physical exercise on metabolic and pancreatic changes induced by experimental diabetes.

  • Leader : TELMA DE JESUS SOARES
  • MEMBRES DE LA BANQUE :
  • ALEX RAFACHO
  • FERNANDA ORTIS
  • LILIANY SOUZA DE BRITO AMARAL
  • RAILDO DA SILVA COQUEIRO
  • TELMA DE JESUS SOARES
  • Data: 2 déc. 2022


  • Afficher le Résumé
  • Introduction. The mechanisms by which exercise promotes its beneficial effects in the pancreas have not yet been fully elucidated in type 1 diabetes mellitus. Aim. The study of exposure factors and physical exercise analyzed initiated previously aims at a diabetes treatment on metabolic and pancreatic changes, as expressions of presentation factors and injury markers, to oxidative stress in pancreatic tissue, correlating these changes to the functions of the pancreas. producer of insulin-producing cells. Methods. Thirty female Wistar rats, weighing between 290 and 310 g, divided into 5 groups: SC (sedentary control, n=6), TC (trained control, n=6), SD (sedentary diabetic, n=6), TD (trained diabetic, n=6) and PTD (previously trained diabetic, n=6). Only the D+PEx group was submitted to 4 weeks of exercise before the induction of diabetes by streptozotocin (40 mg/kg, iv). After confirming of diabetes, the PTD, TD and TC groups were submitted to 8 weeks of exercise. Pancreatic tissue was collected for studies of oxidative stress, immunohistochemical, ELISA and Western Blot. Results. Moderate aerobic exercise improved metabolic control and reduced oxidative/nitractive stress, inflammation, apoptosis and SIRT 1 expression in the pancreatic islets of diabetic rats in the TD and PTD groups compared to sedentary rats the SD group (p<0.05). Both groups of diabetic animals submitted to exercise showed an improvement in the lipid profile marked by a reduction in total cholesterol and plasma triglycerides, LDL-c and VLDL-c with an increase in HDL-c leading to a reduction in the atherogenic index, compared to sedentary diabetic animals (p<0.05). Only the PTD group had reduced Nrf2 (p<0.05) and HO-1 expression (p<0.05), reduced IL-10 levels and increased IL-6 levels and (p<0.05), greater physical capacity and prevented weight loss, decrease in pancreatic insulin, and increase in plasma TBARS levels. Exercise protocols reduced the lipid peroxidation and expression of nitrotyrosine, antioxidants enzymes (catalase and GPx), totals nitrites and TNF in the pancreas of SD and PTD groups compared to the SD group (p<0.05). Nrf2 protein expression was positively correlated with pancreatic levels of TBARS (P < 0.0001) and nitrites (P < 0.01). The HO-1 protein expression (P < 0.0006) was positively correlated with pancreas TBARS levels. Exercise also reduced apoptosis by inhibiting the pro-apoptotic factors Bad, Bax and caspase-3 and increasing the anti-apoptotic marker Bcl2, in addition to improving protein expression and number of SIRT1-positive cells in the DS and DPT groups (p <0.05). SIRT1 expression was observed to negatively correlated with TNF (P<0.0091) and TBARS (P<0.0386) levels in the pancreas. Conclusion. Our data demonstrate that moderate exercise promoted beneficial effects in the pancreas by reducing lipid peroxidation, inflammatory process and apoptosis in female rats with type 1 diabetes.

5
  • Luciano Evangelista dos Santos Filho
  • Influence of the high-protein ketogenic diet associated or not with exercise on glycemic homeostasis and hepatorenal alterations in obese Wistar rats.

  • Leader : AMELIA CRISTINA MENDES DE MAGALHAES GUSMAO
  • MEMBRES DE LA BANQUE :
  • AMELIA CRISTINA MENDES DE MAGALHAES GUSMAO
  • LILIANY SOUZA DE BRITO AMARAL
  • RAFAEL PEREIRA DE PAULA
  • RAILDO DA SILVA COQUEIRO
  • LUIZ CARLOS CARVALHO NAVEGANTES
  • Data: 15 déc. 2022


  • Afficher le Résumé
  • Objective: To evaluate the effects of a high-protein ketogenic diet on parameters related to glycemic homeostasis and hepatorenal alterations in obese Wistar rats submitted or not to exercise. Methods: Forty male Wistar rats weighing between 150 and 200g were used, which initially received control (n=6) or hypercaloric (n=34) diets to induce obesity for 8 weeks. After this period, the animals of the control group (n=6) and part of the hypercaloric group (n=6) were euthanized, with the remaining obese animals subdivided into four groups, receiving diets and submitted or not to moderate-intensity physical exercise for 12 weeks: hypercaloric and sedentary (n=7); hypercaloric and exercised (n=7); high-protein ketogenic and sedentary (n=7); high-protein ketogenic and exercised (n=7). Food intake, body composition and adiposity parameters, blood pressure, serum biochemical and inflammatory profile, glycemic homeostasis, insulin resistance and sensitivity were evaluated. In addition, we evaluated the expression of IR, AMPK, Akt, GSK3β and GLUT4 in muscle, kidney and liver function, morphometric, inflammatory and oxidative profile of the kidneys, fat deposition in the liver, morphology, oxidative stress and immunostaining of insulin and glucagon in the pancreas. Results: The diet-induced obesity model was validated. The treatment of obesity with a high-protein ketogenic diet and/or exercise for 12 weeks determined a reduction in food and caloric intake, body mass gain and adiposity. Despite the increase in blood glucose, the combination of diet and exercise reduced serum insulin, and attenuated peripheral resistance indicators. Isolated exercise increased glucagon expression and reduced insulin in the pancreas, increased IR, GLUT4 and GSK3β expression in muscle. Diet and exercise altered indicators of systemic inflammation, serum lipid profile and liver function markers, in addition to reducing macrovesicular lipid deposition in the liver, improving the oxidative profile in the pancreas and attenuating lipid peroxidation in the kidney. The high-protein ketogenic diet, by itself, promoted changes in kidney function and inflammation, without inducing significant structural changes. Conclusion: The high-protein ketogenic diet associated or not with exercise for 12 weeks had a positive impact on the reduction of body mass and adiposity and fat deposition in the liver, but did not allow confirmation of the improvement in glycemic homeostasis, insulin response and lipid profile. Pancreatic and hepatorenal alterations seemed discreet and insufficient to determine positive or negative effects, thus, further investigations are required, especially of the related metabolic pathways. In this sense, caution is suggested in the use of this diet, even when associated with exercise, since some gaps were evidenced, especially with regard to glycemic homeostasis and impairment of renal function due to proteinuria.

2021
Thèses
1
  • Caroline Vieira Gonçalves
  • Inflammaging and adipose tissue:  New insights in diabetic and hipertensive elderly men

  • Leader : ROBSON AMARO AUGUSTO DA SILVA
  • MEMBRES DE LA BANQUE :
  • DENISAR PALMITO DOS SANTOS
  • LILIANY SOUZA DE BRITO AMARAL
  • ROBSON AMARO AUGUSTO DA SILVA
  • Data: 11 juin 2021


  • Afficher le Résumé
  • INTRODUCTION/OBJECTIVE: The combination of increasing metabolic risks and an aging population will likely continue to drive the growing trends in Chronic Non-Communicable Diseases (NCDs) globally. Systemic arterial hypertension (SAH) and type 2 diabetes mellitus (DM2) are highly relevant NCDs due to the high mortality in the elderly population. Despite the different organs and systems involved has a common risk factor: clinically inflammation silence low-grade. This inflammation has as its principal factor the excess of adipose tissue. In this sense, this work aimed at the expanded study of anthropometric, biochemical, and inflammatory markers of elderly with SAH and DM2. METHODS: The study involved the evaluation of 49 men aged 60-80 years with SAH and DM2. The divided groups according to BMI into eutrophic elderly (EE, n = 24) or overweight elderly (OE, n = 25). Bioimpedance analysis was used to collect anthropometric data. Blood collection was performed to analyze inflammatory and biochemical data. The serum obtained was evaluated by enzymatic assays. RESULTS: Although most of the elderly undergo drug treatment for diabetes and hypertension, they did not have their blood glucose and blood pressure levels controlled. Overweight elderly had a higher glycemic index (p = 0.0201). All the anthropometric data analyzed showed statistically significant differences when compared between groups. There was an increase in most anthropometric markers in overweight elderly. In contrast, in this same group, there was a decrease in the values of lean mass (p <0.0001), bone mass (p <0.0001), water (p <0.0001) and basal metabolism (p = 0.001). Overweight elderly had higher averages for all analyzed inflammatory cytokines. These include: IL-17A (p = 0.0154), IL-1β (p = 0.0376), INF-y (p = 0.0442) and TNF-α (p = 0.0064). In contrast, there was a decrease in the anti-inflammatory cytokine IL-10 (p = 0.0367) in overweight elderly. Also, we observed an increase in the IL-10/IL-17A ratio in eutrophic elderly about overweight elderly. The correlation patterns for biochemical, inflammatory, and body composition variables are different between groups. The correlations are more intense in the eutrophic elderly, especially concerning inflammatory variables and the fat mass variable. CONCLUSION: Although the overweight elderly has an increase in inflammatory parameters, the intensity of their correlations with anthropometric and biochemical parameters are less evident. Also, we found that the pattern of influence of these cytokines is quite different about body composition.

Thèses
1
  • RAFAELA DE SOUZA BITTENCOURT
  • Evaluation of the influence of estradiol on immune response mechanisms in monocytes/macrophages induced by Gardnerella vaginalis

  • Leader : LUCAS MIRANDA MARQUES
  • MEMBRES DE LA BANQUE :
  • CLARISSA LEAL SILVA E SOUZA
  • LILIANY SOUZA DE BRITO AMARAL
  • LUCAS MIRANDA MARQUES
  • SAMIRA ITANA DE SOUZA
  • TELMA DE JESUS SOARES
  • Data: 16 déc. 2021


  • Afficher le Résumé
  • Gardnerella vaginalis is a commensal bacterium of the vaginal microbiota and the main agent of bacterial vaginosis (BV), a vaginal infection established due to an imbalance in this ecosystem. The pathogenesis of bacterial vaginosis is not well established; however, it is considered the main vaginal disorder that affects women of reproductive age, which may hypothesize the influence of female sex hormones in its pathogenesis. Objective: To evaluate the influence of 17β-estradiol (E2) on the immune response induced by Gardnerella vaginalis in in vitro models of female murine peritoneal macrophages (MPMs) and human peripheral blood monocytes (hPMs) from women, with or without physiological ovarian activity. Methodology: in vivo and in vitro experiments were carried out. For the in vivo experiments in animals, the following were performed: body weight, uterine index and estradiol dosage; and in humans, laboratory tests such as blood count, biochemical and hormonal tests were performed. For the in vitro experiments, peritoneal macrophages from BALB/C sham surgery (SHAM) or ovariectomized (OVX) females and human peripheral blood monocytes (hPMs) from fertile and menopausal women were subdivided into three groups: cells inoculated with G. vaginalis, cells with sterile saline, both for 6 hours, and cells pretreated with 17β-Estradiol (E2), for 6 hours, and inoculated with G. vaginalis, also for 6 hours. Inflammatory markers such as: cytokines GM-CSF, IL-1β, TNFα, IL-6, IL-12, IL-23, IL-27 and IL-10, total nitrites, hydrogen peroxide (H2O2), were measured in culture supernatant, and the expression of TLR-2, NF-kB and ERα and ERβ genes. In addition, a growth curve was performed in two groups. Group one, with only G. vaginalis and group two, G. vaginalis with 17β-estradiol, for a period of 24 hours. Results: For the analysis of the growth curve, the inhibitory activity of E2 on G. vaginalis can be verified. For animal experiments: In vivo, SHAM females had higher uterine weight and higher estradiol concentration, while OVX females had higher body weight. In vitro, the concentration of cytokines, IL-6, IL-8, IL-10 and inflammatory markers, total nitrites and (H2O2), showed high levels in MPMs of SHAM and OVX females inoculated with G. vaginalis when compared to G. vaginalis with sterile saline. When treated with E2, the MPMs of OVX females showed higher levels of IL-10 and hydrogen peroxide, when compared to untreated OVX. However, only the hydrogen peroxide matched the MPMs of the SHAM females. Similar results were observed for gene expressions of TLR-2, NF-kB and ERα and ERβ in the SHAM and OVX models between infected and sterile saline. Comparisons between infected cells from the SHAM, OVX and OVX treated with E2 models also showed higher levels of cytokines and inflammatory markers and gene expressions for cells from the SHAM model, with the exception only for the expression of ERβ. For the human experiments: In vivo, all selected research subjects were healthy, but a higher concentration of glucose, total cholesterol, LDL and TGP was observed in menopausal women and a higher concentration of leukocytes in women in their fertile period. For the serum dosage of sex hormones, it was observed that women in the fertile period had higher concentrations of 17β-estradiol and progesterone, while women in menopause had high concentrations of follicle-stimulating (FSH) and luteinizing (LH) hormones. In vitro, hPMs infected with G. vaginalis from women in the reproductive period and menopause showed higher levels of total nitrites, H2O2 and cytokines when compared to saline. However, infected hPMs from menopausal women had higher levels of H2O2 compared to hPMs from women in the reproductive period. With regard to cytokines, cells treated with E2 did not match those with endogenous E2, except for IL-10. Conclusion: In animal and human experiments, in relation to the influence of E2 on the acute inflammatory response to G. vaginalis, it is observed that the hormone has an immunomodulatory characteristic, but it cannot be exclusively defined as pro or anti-inflammatory. In this study, for endogenous E2, all cytokines, inflammatory markers and gene expressions showed higher levels, both in MPMs and hPMs. When treated with E2, MPMs from OVX females and hPMS from menopausal women showed similar response for IL-10 levels in relation to cells with endogenous E2, indicating an anti-inflammatory action. However, acute inflammation recognition and triggering genes also showed similarity between MPMs treated with E2 and cells with exogenous E2. Physiological influences, such as endogenous progesterone, may contribute for cells to present characteristics of an acute inflammatory response, and the treatment of cells, exclusively with E2, has not resulted in an equivalence of cell response with endogenous sex hormones. However, E2 showed a bacteriostatic characteristic in relation to G. vaginalis proliferation, and this hormone can modulate virulence factors of this microorganism, thus contributing to an absent or discrete immune response in the course of bacterial vaginosis.

2020
Thèses
1
  • MAIARA RAULINA DE JESUS DIAS
  • Effects of exercise on morphological and functional changes in the pancreas and liver in an animal model of aging and obesity.

  • Leader : AMELIA CRISTINA MENDES DE MAGALHAES GUSMAO
  • MEMBRES DE LA BANQUE :
  • AMELIA CRISTINA MENDES DE MAGALHAES GUSMAO
  • FABRICIO FREIRE DE MELO
  • RAILDO DA SILVA COQUEIRO
  • ROBSON AMARO AUGUSTO DA SILVA
  • Data: 31 janv. 2020


  • Afficher le Résumé
  • Objectives: To evaluate the effects of preventive and therapeutic exercises on pancreatic and hepatic morphology and function of Wistar rats in an aging and obesity model. Methods: Twenty four male Wistar rats (initial age = 4 months and final age = 14 months) were randomly assigned to three experimental aged and obese groups (n = 8 / group): sedentary, therapeutic exercise, preventive exercise. Body composition parameters, plasma concentration and immunostaining of pancreatic insulin, markers of tissue inflammation, lipid peroxidation, activity and immunostaining of antioxidant enzymes and parameters of pancreatic and hepatic structure were evaluated. Results: Only preventive exercise improved the parameters of body composition and plasma insulin concentration. Pancreatic histology showed that therapeutic and preventive exercises increased the density of pancreatic islets, but had no effect on the islet area and smaller diameter. Analysis of pancreatic and hepatic parameters indicated that only preventive exercise reduced macrophage infiltration into the pancreas and both therapeutic and preventive exercise reduced macrophage infiltration in the liver. In addition, preventive and therapeutic exercise animals had lower immunostaining for insulin Factor Nuclear Kappa B (NF-kB) and Transforming Growth Factor Beta (TGF-b) in the pancreatic parenchyma, as well as lower hepatic and pancreatic tissue lipid peroxidation, with the effect being significantly higher in the preventive exercise group. Both exercise protocols promoted smaller area of fibrosis, increased activity of catalase and Glutathione peroxidase (GPx) enzymes and increased immunostaining for Heme oxygenase 1 (HO-1) in both pancreas and liver, and preventive exercise had a greater effect on these variables. Macrovesicular steatosis was lower in animals submitted to both types of exercise protocol; however, microvesicular steatosis was not different between experimental groups. Conclusion: The beneficial effects of exercise, especially preventive exercise, on body adiposity, insulinemia, morphology, inflammation and redox stress in the liver and pancreatic parenchyma under combined conditions of aging and obesity are promising in preventing degenerative processes in these organs under both conditions.

2
  • MARIA POLIANA LEITE GALANTINI
  • The sweet fuel of inflammation: new looks in the complex web that interconnects diabetes and hypertension

  • Leader : ROBSON AMARO AUGUSTO DA SILVA
  • MEMBRES DE LA BANQUE :
  • AMELIA CRISTINA MENDES DE MAGALHAES GUSMAO
  • LAIZE TOMAZI
  • ROBSON AMARO AUGUSTO DA SILVA
  • Data: 31 janv. 2020


  • Afficher le Résumé
  • Noncommunicable chronic diseases (NCDs) account for about 70% of all deaths worldwide. In this scenario, systemic arterial hypertension (SAH) and type 2 diabetes mellitus (DM2) are diseases that have several aspects in common. These biomarkers provide an understanding of disease processes and can benefit early detection, treatment and management. Thus, the aim of this study was to evaluate serum biomarker concentrations in serum of patients with different severities of DM2 and SAH as well as to analyze the correlations between interleukins and disease severity. Initially, patients previously diagnosed with DM2 and hypertension were stratified into different degrees of disease, aiming to detect the factors that most influence the complications of the aforementioned diseases. The groups were divided into low risk (1), moderate risk (2), high risk (2), very high risk (4), according to the European Society of Cardiology, which correlates blood pressure values with the presence of of risk factors. To perform this work, volunteers were recruited for pressure measurement and body composition analysis was performed through bioimpedance. Blood was collected from these patients for biochemical measurements and ELISA to detect serum concentrations of cytokines IL-17, IL-1β, IFN-γ, TNF-α and IL-10. Statistical analyzes were performed using the Kruskal-Wallis test, and correlations were analyzed using the R Studio software. We observed that the higher the severity, the higher the serum concentration of proinflammatory cytokines, however, no significant difference was observed between sexes or climacteric period. Strong positive correlations were found between IL-17, IL-1β and IFN-γ of the low risk group, and these correlations are lost as the risk group increases. These findings suggest that inflammation is present contributing to the worsening of hypertension and DM2. Through Bayesian analyzes we found hyperglycemia playing a central role in modulating the proinflammatory state. This state can be changed with the practice of physical activity, confirming its beneficial and protective effect. This is the first paper that shows the complex interaction between different biomarkers in DM2 and SAH, especially hyperglycemia as inflammation inducer, and how the interaction of these markers increases disease severity.

3
  • TALITA COSTA DOS SANTOS
  • Evaluation of anti-inflammatory, antinociceptive, antioxidant and toxicological activity of the ethanolic extract and bark fractions of Peltogyne pauciflora Benth. 

  • Leader : REGIANE YATSUDA
  • MEMBRES DE LA BANQUE :
  • REGIANE YATSUDA
  • LUCAS MIRANDA MARQUES
  • ÉRIKA PEREIRA DE SOUZA
  • Data: 30 juil. 2020


  • Afficher le Résumé
  • Peltogyne pauciflora Benth (Leguminosae), is a caatinga plant in Brazil, popularly known as buranhê and imburanhê, and the infusion of the bark is used to treat "inflammation and pain in the spine". The objective of this study was to evaluate the ethanolic extract of P. pauciflora bark and its fractions regarding its chemical constitution, anti-inflammatory, antinociceptive, antioxidant and toxicological activity. The bark was collected in the Contendas Sincorá National Forest and were macerated in ethanol, obtaining the ethanolic extract (EEPP, doses 50, 100 and 200 mg/kg), being later partitioned, originating the hexane (H), dichloromethane ( DM), ethyl acetate (AE) and butanol (B) fractions, all the doses at 50 mg/kg. EEPP, H and DM fractions were analyzed by GC-MS, and carbohydrates, fatty and phenolic compounds were identified, being highlighted the bioactive substances: beta-sitosterol, campesterol, lupenone, lupeol, 3-methoxy-4 acid hydroxybenzoic acid, phytol, oleic acid, ethyl linoleate and palmitic acid. EEPP, H, DM and AE fractions contain high content of total phenolics. For anti-inflammatory, antinociceptive and antioxidant tests, adult male Balb/c mice were used. In abdominal contortion test induced by 0.6% acetic acid, EEPP (50 and 100 mg/kg), H, DM and AE fractions reduced the nociceptive responses in relation to the vehicle group (VH) (p <0.05). In the nociception test induced by intraplantar injection of 1.5% formalin, EEPP (50 and 100 mg/kg), H and DM fractions reduced the number of flinches in both phases (neurogenic and inflammatory), and AE fraction reduced only in the inflammatory phase in relation to VH (p <0.05), and besides, the paw edema was reduced by EEPP (100 mg/kg). In the Von Frey test, EEPP (50 and 100 mg/kg), DM and AE fractions reduced hypernociception in relation to VH (p <0.05). Myeloperoxidase production by neutrophils decreased with EEPP (50, 100, 200 mg / kg), H, DM and AE fractions compared to VH (p <0.05), as well as the lipid peroxidation determined by the test of reactive substances thiobarbituric acid (TBARS) (p <0.05). EEPP (50, 100 and 200 mg/kg) and H, DM and AE fractions decreased the expression of the TNF-α and IL-6 genes, and only EEPP (200 mg/kg) reduces the expression of the IL-17 gene (p <0.05). EEPP (100 mg/kg), H and DM fractions reduced the vascular permeability in the Evans blue test (p <0.05). EEPP (50, 100 and 200 mg/kg), H and DM fractions reduced the levels of neutrophils in the peritoneal cavity (p <0.05), as well as reducing the levels of nitrite production (p <0.05). In the lethality test against Artemia salina L., EEPP presented moderate toxicity and the fractions were considered inactive. This is the first phytochemical and biological study report of the bark ethanolic extract of P. pauciflora and its H, DM and AE fractions, which have antioxidant, antinociceptive and anti-inflammatory activities, being a promising natural source for clinical use and identification of new compounds. In the future, studies will be carried out to identify bioactive compounds and mechanisms of action, in addition to toxicological assessment with determination of the lethal dose in vivo.

4
  • DANILO NASCIMENTO LOPES
  • Effect of preventive exercise on pancreatic changes induced by type 1 diabetes mellitus in ovariectomized rats.

  • Leader : TELMA DE JESUS SOARES
  • MEMBRES DE LA BANQUE :
  • LILIANY SOUZA DE BRITO AMARAL
  • SAMIRA ITANA DE SOUZA
  • TELMA DE JESUS SOARES
  • Data: 15 déc. 2020


  • Afficher le Résumé
  • One of the main changes in type 1 diabetes mellitus (T1DM) is the progressive reduction of the pancreatic β cells, and consequently insulin production. Lipid peroxidation, pro-inflammatory cytokines, and nuclear transcription factor (NF-kB) play an important role in β cell dysfunction and death during T1DM. In addition, the transforming growth factor (TGF-β1) and fibrosis participate in the development of diabetes mellitus. The beneficial effects of physical exercise on complications in various organs resulting from DM have been demonstrated. However, there are no studies evaluating the effects of exercise on islet of langerhans of diabetic ovariectomized rats. For this, wistar rats were anesthetized and submitted to bilateral ovariectomy. After surgical recovery, the animals were injected with 40 mg/kg streptozotocin (STZ) for the induction of DM1 or 0.1M citrate buffer, pH 4.5, and were divided into four experimental groups: 6 sedentary control rats OVX (SCO); 6 previously trained OVX controls (PTCO); 6 sedentary diabetic OVX (SDO); and 6 previously trained diabetic OVX (PTDO). The animals of the PTDO and PTCO groups were submetted four weeks of aerobic training previous to induction of T1DM. After four weeks, T1DM induction was performed in the animals of the SDO and PTDO groups. Then, the PTCO and PTDO groups were submitted to the same protocol of regular aerobic physical exercise of moderate intensity, which consisted of running on a motorized treadmill for a period of eight weeks. Physical exercise did not increase the insulin content and mass of β cells in the islets of langerhans in the PTDO group. However, it decreased the content of glucagon and α cell mass, showing the beneficial effect of exercise on the counter-regulating hormone of blood glucose homeostasis. In addition, blood glucose from PTDO rats was lower than that of SDO rats. Physical exercise also decreased TGF-β1 expression in PTDO rats compared to SCO rats, as well as decreased fibrosis in these islets. Physical exercise reduced nitrative stress by reduced nitrotyrosine expression in the PTDO group. In addition, physical exercise had a fundamental effect in reducing the expression of the transcription factor NF-kB. These results show the beneficial effect of physical exercise prior to the induction of diabetes on the expression of inflammatory and oxidative markers, islet structure and content of the counter-regulating hormone of blood glucose concentration.

Thèses
1
  • RAFAEL SANTOS DANTAS MIRANDA DÓREA
  • EVALUATION OF ANTI-INFLAMMATORY, ANTINOCICEPTIVE AND HEALING ACTIVITY OF THE ETHANOLIC EXTRACT AND SUBFRACTIONS OF THE LEAF OF Schinopsis brasilensis ENGLER

  • Leader : REGIANE YATSUDA
  • MEMBRES DE LA BANQUE :
  • BRUNO OLIVEIRA MOREIRA
  • DAIANA SILVA LOPES
  • GUILHERME BARRETO CAMPOS
  • LUCAS MIRANDA MARQUES
  • REGIANE YATSUDA
  • Data: 6 févr. 2020


  • Afficher le Résumé
  • Schinopsis brasiliensis Engler, popularly known as “Braúna”, is widely used in folk medicine to treat pain, fever, cough and other diseases. This study aimed to evaluate the antinociceptive, anti-inflammatory and healing activity of S. brasiliensis Engler from Bahia semi-arid, collected in the region of the National Forest Contendas do Sincorá (FLONA), according to ethnopharmacological data of the region. Previous tests carried out with the crude extract (ethanolic) and fractions have already proven the antinociceptive and anti-inflammatory action present in Brauna leaf. Thus, the aim of this study was to evaluate the antinociceptive and anti-inflammatory activity of S. brasiliensis leaf subfractions, to initiate the identification process of bioactive compounds, as well as to elucidate the possible mechanisms of action of these subfractions. The results were obtained through the collection and identification of plant species, phytochemical analysis, ethanolic extract preparation, fractions and subfractions, isolation and identification of compounds. The subfractions tested were hexane (H1, H2, H3, H4) and dichloromethane (D1, D2, D3, D4 and D5). To evaluate antinociceptive and anti-inflammatory activity, tests for abdominal acetic acid-induced writhing, leukocyte recruitment into the peritoneal cavity, evaluation of Evans blue peritoneal extravasation, nociception induced by formalin injection were performed. For chronic inflammation, the granuloma test induced by subcutaneous cotton pellet implantation was used. An experimental excisional wound model was performed to evaluate the healing activity of the leaf extract. For toxicological evaluation, acute toxicity tests were performed in Wistar rats and toxicity against Artemia salina (TAS). Statistical analysis was performed by one-way or two-way ANOVA, parametric approach, followed by Bonferroni's multiple comparison test, with p <0.05. The leaves of S. brasiliensis have polyphenols, tannins, saponins, flavonoids, alkaloids and steroids in both the crude extract and the studied fractions. Gas chromatographic analysis coupled with mass spectrophotometry identified 36 substances in the hexane and dichloromethane fraction, among them Ethyl Galate, a substance of high pharmacological interest. In the acetic acid induced abdominal writhing experiment, subfractions H2, H3, H4 and D1 (50 mg/kg) significantly reduced nociception (p <0.05). The ethanolic extract (100 mg/kg) presented antinociceptive activity with opioid action and inhibitory synthesis of nitric oxide (p <0.05). In the intraplantar formalin injection induced nociception test, subfractions H2, H3, H4, D1, D2, D3, D4 and D5 (50 mg/kg) reduced the number of formalin-induced flinches in phase 1 of the experiment, (p> 0.05) and in phase 2, the subfractions H3, H4, D1, D2, D4 and D5 significantly decreased nociception compared to the vehicle group (p <0.05). None of the subfractions decreased paw edema (p> 0.05). The subfractions D2, D3, D4 and D5 were able to increase the pain threshold of the animals in the Von Frey experiment (p <0.05). The subfractions H2, H3, H4, D1 and D5 (50 mg/kg) showed anti-inflammatory activity reducing the neutrophil migration to the peritoneal cavity (p <0.05), and the possible mechanism of anti-inflammatory action of the H3, H4, D3, D4 and D5 subfractions were due to decreased TNF-a cytokine in treated animals and elevation of IL-10 cytokine when animals were treated with D1 subfraction. There was no decrease in vascular permeability by subfractions evaluated in the Evans blue extravasation test (p> 0.05). Ethanolic extract (50 and 100 mg/kg) and all subfractions tested reduced the weight of granulomatous tissue formed in relation to the control group (p <0.05), similar to the reduction promoted in the dexamethasone group (p> 0.05). The ethanolic extract did not reduce the area of excision wound contraction in rats relative to the vehicle group (p> 0.05). Acute toxicity evaluation revealed changes in hematological, hepatic and renal patterns in animals treated with a single dose of 2000 mg/kg of Braúna ethanolic extract. The cytotoxicity was evaluated against the Artemia saline test and the average dose found was 93 μg/ml, being considered very active. Thus, it can be concluded that S. brasiliensis Engler leaves have relevant therapeutic potential characterized by the presence of compounds with proven activity, as well as having significant antinociceptive and anti-inflammatory activities, and for being safe in the evaluated therapeutic doses. Thus, Brauna leaf is an important natural source for the identification of new molecules and compounds for therapeutic purposes, and can be used by the population in a sustainable way, helping in the environmental protection of the species.

2
  • MANOELA RIOS TRINDADE CARNEIRO
  • Evaluation of galactagogue activity of ethanol extract, fractions and a compound isolated from Pimpinella anisum Lineu seeds in an experimental model with rats. 

  • Leader : REGIANE YATSUDA
  • MEMBRES DE LA BANQUE :
  • AMELIA CRISTINA MENDES DE MAGALHAES GUSMAO
  • DAIANA SILVA LOPES
  • LUCAS MIRANDA MARQUES
  • REGIANE YATSUDA
  • ÉRIKA PEREIRA DE SOUZA
  • Data: 11 déc. 2020


  • Afficher le Résumé
  • Pimpinella anisum Lineu is used to increase the production of breast milk, but is empirically used by mothers with hypogalactia, and its effectiveness, safety, effective dose and mechanisms of action must be proven. This study evaluated the phytochemical profile and galactagogue activity of the ethanolic extract (EEPA), fractions of the seeds of P. anisum and the isolated compound anethole, as well as the toxicity of the EEPA. Lactating Wistar rats breastfeeding seven to eight puppies each, were divided into groups treated daily intraperitoneally with (n = 6): a) 0.4 ml of distilled water; b) EEPA in doses of 12.5; 25 and 50 mg/kg; c) FH doses at 12.5; 25 and 50 mg/kg; d) FD in doses of 12.5; 25 and 50 mg/Kg, e) FAE at doses of 12.5; 25 and 50 mg/kg; f) FB at doses of 6.25; 12.5 and 25 mg/kg; and only g) anethole in doses of 12.5; 25 and 50 mg/kg; orally. The daily and total weight gain of the litter was determined, the estimated milk production in 1 h of breastfeeding, the weight loss of the lactating rat and the breastfeeding time from the 4th to the 18th day of life of the puppies. On the 19th day, rats were milked to determine the energy content and the major constituents of milk, being euthanized on the 20th day and removed the mammary glands for histological analysis. In the 2nd experiment, the prolactin and oxytocin diets were measured in the adenohypophysis or neurohypophysis, serum and mammary gland in the rats on the 14th and 21st day of lactation, divided into the following groups (n = 6): a) 0.4 mL distilled water, b) EEPA (12.5 mg/kg) and c) anethole (50 mg/kg). Toxicity to Artemia salina (12.5; 25; 50, 100 and 200 μg/mL) and acute toxicity with determination of LD50 with male and specific Wistar rats were analyzed for groups (n: 3): a) ethanol 10%, b) 5, 50, 300 and 2000 mg/kg of EEPA; and c) 0.4 ml distilled water. Galactagogue activity was observed only with EEPA (12.5 mg/kg), fraction of dichloromethane (25 mg/kg) and anethole (50 mg/kg), as there was greater daily weight gain (24.8%, 11, 6%, 10.2%) and total (28.1%, 11.37%, 9.7%), and estimated milk production (32.6%, 40%, 22.4%) (p < 0.05), without changes in the weight loss of the lactating rat and without breastfeeding time (p> 0.05) in relation to the control. EEPA increased the concentration of total proteins and cholesterol (84.7% and 185%), FD increased the concentration of lactose, total lipids and cholesterol (27.6%, 140.4% and 140%) and anethole increased all constituents in relation to the control (p <0.05). Although the mammary glands were histologically in process of involution, the smaller number of lobes and alveoli of the EEPA and the smaller number of alveoli of the FD and anethole indicate that they were distended and the gland was more active previously. The highest levels of adenohypophyseal, serum and mammary gland prolactin at 21 days were found with EEPA and anethole (p <0.05). Increased oxytocin concentration occurred on the 14th day in the neurohypophysis, and in the EEPA serum and only in the anethole neurohypophysis. EEPA has no acute toxicity or animal death. Thus, as seeds of P. anisum have galactagogue activity attributed to the presence of compounds with estrogenic activity (β-sitosterol, stigmasterol, anethole and their polymers) and dopamine antagonists (anethole) that stimulate a greater production of prolactin, when it comes to histological changes of the mammary gland, constituents and quantity of milk, reflecting the greater growth of the litter.

2019
Thèses
1
  • ISRAEL SOUZA RIBEIRO
  • Nutritional status alters inflammatory balance in diabetic and hypertensive elderly women

  • Leader : ROBSON AMARO AUGUSTO DA SILVA
  • MEMBRES DE LA BANQUE :
  • ROBSON AMARO AUGUSTO DA SILVA
  • LILIANY SOUZA DE BRITO AMARAL
  • FABRICIO FREIRE DE MELO
  • Data: 26 juin 2019


  • Afficher le Résumé
  • Introduction/Objective: In women, aging is evidenced by physiological hormonal alterations that trigger changes in body composition, emergence of chronic low-grade inflammation, which is an important pre-disposition to the development of chronic diseases such as Systemic Arterial Hypertension (SAH) and Type 2 Diabetes Mellitus (T2DM). Although it is a strong pro-inflammatory nature disorder, little is known about how body composition interferes with inflammatory markers in diabetic and hypertensive elderly women. Therefore, this study’s objective was to evaluate the inflammation in diabetic and hypertensive elderly women, and their association with fat mass. Methods: It comprised the evaluation of 144 women aged between 60 and 80 years old, diagnosed with SAH and T2DM, assisted by Family Health Units in Vitória da Conquista, Bahia, Brazil. According to body mass index (BMI), these women were classified as either eutrophic or overweight. Then, anthropometric evaluations of different markers were performed, as well as peripheral blood collection for the measurement of serum concentrations of biochemical markers and cytokines. Finally, the groups were compared through the Mann-Whitney non-parametric test and the Spearman correlation test was performed through the Corrplot analysis package of the statistical software R, with an increased evaluation of the influence of body composition on the factors analyzed. Results: In the eutrophic females, the IL-10/IL-17A ratio was increased when compared to those overweight. In addition, IL-17 correlated negatively with HDL and positively with total cholesterol, LDL, triglycerides, VLDL, and glucose in the eutrophic ones, but not in the overweight individuals. IL-10 also showed differences in the correlation pattern observed between the groups, since for this eutrophic cytokine, it presented positive correlation with the waist circumference, waist/height ratio, and negative association with IL-17, while in overweight elderly women, it was not observed such pattern. Conclusion: Hence, this work demonstrates how the amount of fat mass interferes with the balance of cytokines, especially IL-10 and IL-17, and how it may exert an effect on biochemical parameters and risk factors associated with T2DM and SAH.

2
  • ÍTALO SOUSA PEREIRA
  • HEADS OR TAILS: MIGHT PHYSICAL ACTIVITY BE MORE IMPORTANT THAN ONE AGE IN MEN 
    WITH DIABETES AND HYPERTENSION?
  • Leader : ROBSON AMARO AUGUSTO DA SILVA
  • MEMBRES DE LA BANQUE :
  • ROBSON AMARO AUGUSTO DA SILVA
  • TELMA DE JESUS SOARES
  • VIVIAN FRANCIELLE FRANCA
  • Data: 26 juin 2019


  • Afficher le Résumé
  • INTRODUCTION / OBJECTIVE: Systemic arterial hypertension (SAH) and type 2 diabetes mellitus (T2DM) are two important chronic noncommunicable diseases (NCDs) responsible for a high worldwide mortality associated with a high cardiometabolic risk. Aging is marked by a broad spectrum of physiological changes that configure the elderly as a risk group for the development of NCDs. Drug therapy for SAH and DMT2 is often accompanied by physical activity, and this approach is associated with the reduction of cardiometabolic risk associated with these comorbidities. However, little is known about the existence of distinct therapeutic benefit profiles of physical activity among elderly and middle-aged hypertensive and diabetic men. Therefore, the objective of this study was to compare pathophysiological markers of SAH and DMT2 among middle-aged and elderly individuals, while physical activity practitioners or sedentary. METHODS: In this study, 94 men with SAH and DMT2 were included. The work involved the application of the International Physical Activity Questionnaire (IPAQ) and the Quality of Life and Health Assessment Questionnaire (QVS-80). A blood sample was collected from the participants and an anthropometric evaluation was performed. the practice of physical activity was defined by at least 150 minutes of physical activity per week for a period of at least three months. Individuals older than or equal to 60 years were classified as elderly. Blood samples were submitted to biochemical (HDL, LDL, VLDL, triglyceride and fasting glucose), hormonal (total testosterone and estradiol) and immunological analysis (IL-1β, IL-17, IFN-γ, TNF-α and IL-10). RESULTS: Physical activity practitioners presented higher lean mass and bone mass, as well as lower fat mass than sedentary individuals. The lean mass participated in an axis of multiple negative correlations with pathological markers of SAH and DMT2, correlating negatively with the ratio between waist circumference and height, fat mass, and body mass index. In physically active elderly, lean mass still correlated negatively with systemic inflammatory markers and positively with IL-10 and serum estradiol. Physical activity subjects also had lower serum concentrations of LDL, VLDL, triglycerides and fasting glucose. Physically active elderly exhibited lower serum concentrations of IL-1β and TNF-α than sedentary middle-aged men, as well as lower serum concentrations of IL-17, IL-1β, TNF-α and IFN-γ than its sedentary counterpart. In this study we detected differences between the serum concentrations of testosterone and estradiol between the groups. CONCLUSION: Together, our results suggest that, for men with SAH and DMT2, the practice of physical activity is more valuable than the aging phenom in the modulation of pathophysiological markers of these SAH and DMT2, mainly because it participates in the regulation of the systemic inflammation observed in these comorbidities. However, the practice of physical activity has shown to be beneficial for both middle-aged and elderly diabetic and hypertensive men, being associated with have a lower cardiovascular risk in the pathogenesis of these diseases. 

3
  • Thiago Macêdo Lopes Correia
  • Effects of physical training on protection against cigarette smoke-induced oxidative stress and muscle inflammation.

  • Leader : RAFAEL PEREIRA DE PAULA
  • MEMBRES DE LA BANQUE :
  • AMELIA CRISTINA MENDES DE MAGALHAES GUSMAO
  • RAFAEL PEREIRA DE PAULA
  • JOSÉ AILTON OLIVEIRA CARNEIRO
  • Data: 17 sept. 2019


  • Afficher le Résumé
  • Objective: To investigate the effects of physical training on changes in physical performance, antioxidant capacity and gene expression of inflammatory markers in skeletal muscle of mice exposed to cigarette smoke (CS). Methods: Thirty-eight eightweek-old male C57 / BL6 mice were randomly divided into four groups (n = 8 / group), submitted or not to CS and physical exercise: sedentary (SED), SED + CS, trained (TRE). and TRE + CS. All animals underwent the maximum progressive swimming test to assess aerobic capacity and inverted screen test for muscle endurance assessment. Total body mass (TBM) and food intake were verified weekly throughout the experiment. After euthanasia, visceral adipose tissue (TAV) deposits and gastrocnemius muscles were collected and weighed. TAV was used to calculate adiposity index and muscle were for glutathione peroxidase and catalase activity assays and expression of genes encoding protein markers of inflammation. Results: Food intake increased between the initial (1st to 4th week) and final (5th to 8th week) measurements in all groups. The comparison between the groups indicated that the mice exposed to cigarette smoke had lower food consumption when compared to the SED group, with no statistical difference compared to the TRE group. There was a reduction in TBM between the initial and final measurements only in the groups exposed to cigarette smoke (SED + CS and TRE + CS). Comparison of TBM between groups showed no significant difference between them. Carcass weight and adiposity index were lower in the SED + CS group compared to the other groups. Forced swim test performance improved between initial and final measurements in all groups. The comparison between the groups showed that the TRE group presented better performance when compared to the other groups; On the other hand, the SED + CS group presented worse performance when compared to the other groups, while the SED and TRE + CS groups did not present statistical difference. Performance in the inverted screen test improved between initial and final measurements in the TRE group only. The comparison between the groups showed that the TRE group presented better performance when compared to the other groups, while the SED, SED + CS and TRE + CS groups did not present statistical difference. Catalase enzyme activity was statistically higher in the TRE group compared to the other groups. For GPx enzyme, no significant difference was observed between the groups. Gene expression analysis indicated that, compared to the other groups, animals from the SED + CS group expressed more TNF-α and MCP-1 and less HO-1. The expression of the IL-10 cytokine gene was higher in the TRE group when compared to the SED and SED + CS groups, while the TGF-β gene expression was higher in the SED + CS group when compared to the TRE group. There was no statistical difference between groups in the expression of IL-1β and IL-6 cytokine-related genes. Conclusion: Four weeks of exposure to cigarette smoke induced a reduction in food intake, accompanied by greater impairment of body mass and composition, as well as reduced physical performance and altered gene expression associated with maintaining or controlling inflammation. In contrast, regular exercise protected animals exposed to smoke from changes in body composition, physical performance, and expression of the TNF-α, MCP-1, and HO-1 genes.

Thèses
1
  • CLARISSA LEAL SILVA E SOUZA
  • Evaluation of the role of the monocyte / macrophage immune response induced by Staphylococcus aureus.

  • Leader : LUCAS MIRANDA MARQUES
  • MEMBRES DE LA BANQUE :
  • AMELIA CRISTINA MENDES DE MAGALHAES GUSMAO
  • GUILHERME BARRETO CAMPOS
  • JESSICA BOMFIM DE ALMEIDA
  • LUCAS MIRANDA MARQUES
  • TELMA DE JESUS SOARES
  • Data: 2 déc. 2019


  • Afficher le Résumé
  • Clinical and experimental evidence supports the hypothesis that sex steroids regulate the immune response and thus exert effects on adverse pathological conditions such as bacterial infections. In general, the hormonal influence paradigm on the immune response stipulates that estrogen increases this response, while testosterone suppresses it. However, data in the literature are still controversial. Still, there is a gap regarding the role of estrogen in infections with Gram-positive bacteria such as S. aureus. The aim of this study was to evaluate the influence of ovariectomy and 17β-estradiol on S. aureus-induced immune response in an in vitro model of murine peritoneal macrophages (MPMs) and human peripheral blood monocytes (hPMs) and in an in vivo model. For this, female BALB / c mice were ovariectomized (OVX) or sham operated (Sham). In the animal model, females were inoculated intraperitoneally with S. aureus ATCC 25923 or sterile saline. The animals were euthanized at 7 different periods with 24-hour interval each and 10 females (n = 5 Sham / n = 5 OVX) were grouped for each period. After euthanasia, blood samples were collected for total and differential leukocyte count and quantification of S. aureus by RT-PCR. The uterus and spleen were removed and weighed. The serum was intended for evaluation of estradiol levels. The lungs were removed and fractionated for immunohistochemical analysis for macrophage detection (anti-CD68) and relative gene expression of IL-6, IL-1β and TNF-α by RT-PCR. The results showed that OVX females had splenomegaly and late monocyte response compared to shams. Intraperitoneal inoculation caused bacteremia in both groups, and OVX females presented late pulmonary recruitment of macrophages. In addition, OVX females showed higher gene expression of IL-1β, TNF-α and IL-6. Higher IL-6 expression compared to sham females was observed even in the absence of infection. In the in vitro model, thioglycolate-induced peritoneal macrophages (2 x 105 ) of female shams (n = 3), OVX (n = 3) and male (n = 3) mice were inoculated with S. aureus for 6 hours. Macrophages obtained from OVX females and males were previously treated for 24 hours with 17βestradiol (E2) (10-7 M). The macrophages were collected and destined to evaluate the relative gene expression of TNF-α, IL-1β, IL-6, IL-8 and TLR2. Results showed that E2 treatment decreased cytokines gene expression, except for IL-8, in which male MPMs showed increased expression. Also, E2 decreases TLR2 receptor gene expression. In the in vitro model of hPMs, six men and six women were selected and hPMs were isolated from peripheral blood samples of the volunteers. In women, blood was collected in both menstrual and fertile periods. After 24h in a CO2 oven, the hPMs were inoculated by S. aureus for 6 hours. After this period, the supernatant was collected for Luminex cytokine analysis and the hPMs removed for analysis of 84 genes involved in host response to bacterial infections by RT-PCR array. Compared to male hPMs, it was observed that E2-treated male hPMs produced less TNF-α, IL-1 and IL-6 and more IL-23, IL-27 and GM-CSF, and women's hPMs in the fertile period produced less TNF-α, IL-1 and produced more IL-10, IL-12, IL-23 and IL-27. Compared to hPMs from women in menstrual period, the hPMs from women in the fertile period produced more IL-12. Male hPMs treated with E2 and hPMs of women in the fertile period expressed less TRL2 than male hPMs. According to the analysis of gene expression it was possible to infer that E2 inhibited the NFκB pathway. It is concluded that estrogen acts as an immunoprotectant by modulating an antiinflammatory action on the immune response induced by S. aureus. Keywords: Sexual dimorphism. 17β-estradiol.

2
  • DENISAR PALMITO DOS SANTOS
  • Evaluation of new photosensitizers for photodynamic therapy in the treatment of intradermal Staphylococcus aureus infection in a murine model 

  • Leader : ROBSON AMARO AUGUSTO DA SILVA
  • MEMBRES DE LA BANQUE :
  • AMELIA CRISTINA MENDES DE MAGALHAES GUSMAO
  • DIRCEU JOAQUIM COSTA
  • FABRICIO FREIRE DE MELO
  • REGIANE YATSUDA
  • ROBSON AMARO AUGUSTO DA SILVA
  • Data: 5 déc. 2019


  • Afficher le Résumé
  • Bacterial infections are a public health problem due to the wide variety of pathogenic microorganisms. Among these, Staphylococcus aureus is the main causative agent of bacterial infections in the world and several strains of this agent are already able to resist conventional drug therapy. In this context, antimicrobial photodynamic therapy (aPDT) appears as a promising tool through microbial inactivation with the use of light. In general, aPDT is applied in treatments involving photosensitizers capable of generating oxygen free radicals that will lead to bacterial clearance. Thus, this work has pioneered the use of Resveratrol and Myrciaria cauliflora extract as photosensitizers in antimicrobial therapy against S. aureus. Methods: In vitro tests were performed to determine the antibacterial activity of blue LED light-activated photosensitizers, as well as experiments with uric acid to verify singlet oxygen formation. Possible structural changes of Resveratrol were evaluated by HPLC. In in vivo assays, the air pocket model was performed in C57Bl/6 mice to evaluate the antimicrobial activity of photoactivated Resveratrol, as well as to evaluate cell migration by histological techniques and cytokine production by ELISA. In another analysis, a model of intradermal infection in the left ear was performed to evaluate the two photosensitizers separately in Balb/c mice. After infection and euthanasia, the ear was collected and the immunohistochemistry technique was used to mark Myeloperoxidase (MPO) and E-cadherin. The lymph node of the animals was removed to evaluate the bacterial load and cytokine production. Results and Discussion: Photoactivated Resveratrol exhibited an increase in MPO labeling and its antibacterial action, possibly caused by singlet oxygen formation. In the air pocket model, TNF-α and IL-17A cytokines were produced, decreasing bacterial load and, consequently, decreasing inflammation after 24 hours of infection. Decreased number of cells in the inflammatory environment was associated with resolution of inflammation along with higher IL-10 production. In addition, it was observed in the ear dermis that photoactivated Resveratrol promoted an increase in MPO production with reduction of bacterial load in the draining lymph node. Regarding Myrciaria cauliflora, a reduction in bacterial load was observed in in vitro tests, with increased production of TNF-α, 17A in the lymph node drainage and MPO in the indradermal site of infection. Conclusion: From the analyzed data, it is possible to predict that Resveratrol and Myrciaria cauliflora extract are promising photosensitizers for antimicrobial photodynamic therapy, especially for the control of bacterial load in intradermal infections caused by S. aureus.

2018
Thèses
1
  • AMANDA ALVES DE ALMEIDA
  • Influence of intensity and weekly frequency of physical training against cysplatin-induced renal injury

  • Leader : RAFAEL PEREIRA DE PAULA
  • MEMBRES DE LA BANQUE :
  • TELMA DE JESUS SOARES
  • RAFAEL PEREIRA DE PAULA
  • JOSÉ AILTON OLIVEIRA CARNEIRO
  • Data: 23 août 2018


  • Afficher le Résumé
  • To investigate the influence of the parameters: intensity and weekly frequency during 8 weeks of aerobic exercise, on the adaptations of the antioxidant defense and functional and structural alterations in the kidneys of mice in a model of acute renal injury induced by cisplatin. Fourty old male Swiss mice at four months of age (16 weeks) were randomly assigned to five experimental groups (n = 8 / group): 1.
    Sedentary, 2. (LI_3X) low intensity training 3 times per week, 3. (HI_3X) high intensity training 3 times per week, 4. (LI_5X) low intensity training 5 times per week and 5. (HI_5X) high intensity training 5 times per week. They practiced forced swimming for 8 weeks and at the end of the training period the antineoplastic Cisplatin was administered in all the experimental groups for induction of acute renal injury. After 96 hours of administration the animals were euthanized and the kidneys, muscles and visceral adipose tissues were removed for further analysis. Body composition parameters, renal structure and function, lipid peroxidation markers and antioxidant enzymes activity, as well as the expression of genes involved in the redox, inflammatory and apoptotic balance pathways were evaluated. The results showed that the weekly frequency of 3 times per week promoted better results in relation to the improvement of renal structure, redox balance and apoptotic processes. It was observed that the group trained in the frequency of 3 times per week, regardless of the intensity, had a greater mass of brown adipose tissue when compared to the other experimental groups. Structurally there were better results related to this same
    frequency with a lower percentage of necrotic tubules, which may have reflected a functional improvement with lower serum urea concentration. There was no significant difference in serum creatinine concentration between the experimental groups. The lipid peroxidation was higher in the sedentary group when compared to the exercised groups, regardless of frequency and intensity. However, catalase activity was higher in all groups compared to the sedentary group. The trained group BI_3X presented higher GPx activity and lower gene expression of NFkB and Caspase-3. There were no significant differences in the gene expression of Nrf2 in any of the experimental groups. Our data demonstrate that weekly training frequency was the parameter of greatest influence on redox balance and apoptosis and inflammation in acute renal injury induced by cisplatin. The results indicate that increased antioxidant capacity in
    renal tissue attenuates the inflammatory process and cell death signaling pathways, which constitute the pathophysiology of acute renal injury induced by cisplatin.

2
  • LORENA LÔBO BRITO MORBECK
  • Evaluation of anti-inflammatory, antinociceptive, antioxidant and toxicological activity of the ethanolic extract and of the stem and bark fractions of Aeschynomene martii Benth.
  • Leader : REGIANE YATSUDA
  • MEMBRES DE LA BANQUE :
  • LUCAS MIRANDA MARQUES
  • REGIANE YATSUDA
  • ÉRIKA PEREIRA DE SOUZA
  • Data: 18 déc. 2018


  • Afficher le Résumé
  • The plant species to be studied, Aeschynomene martii Benth, of the genus Aeschynomene, family of Leguminosae, possess bioactive compounds with great pharmacological potential to be used. The objective of this study was to evaluate the antinociceptive, anti-inflammatory, antioxidant and toxicological activities of A. martii Benth stem and bark, collected in the Contendas do Sincorá National Forest region (FLONA). The ethanolic extract was prepared by maceration and subjected to partition extraction. After evaporation, the four fractions of the crude extract were obtained in the following yields: 13.21% (hexane), 40.92% (dichloromethane), 30.68% (ethyl acetate) and 8.10% (butanol) relative to the weight of the crude extract 17.03 g. The phytochemical exploration of the fractions was performed by CCD with specific developers. Fractions of hexane and dichloromethane had their chromatographic profiles evaluated by GC-MS, with the emphasis on the identification: stigmasterol, b-sitosterol, lupenone, 3,3',4',5,5',7-hexamethoxyflavone, besides the acids fatty acids. The antioxidant activity was evaluated by the DPPH free radical sequestration test, the ethanolic extract and the fractions showed no significant antioxidant activity (p < 0.05), besides being classified as inhibitory concentration (good, medium and low, respectively). For the antinociceptive and anti-inflammatory assays adult male Balb/c mice were used. The antinociceptive effect was evaluated by the following tests: 0.6% acetic acid-induced abdominal contortion, where all fractions (25 mg/kg) promoted a significant reduction in nociceptive responses (p < 0.05). Intraplantar injection of formalin 1.5%, in phases 1 and 2, the fractions (25 mg/kg) reduced the number of flinches in comparison to the negative control (p < 0.05), when compared to the positive control group morphine, dichloromethane and butanol fractions did not present statistical difference (p < 0.05), the paw edema formed significantly reduced in the fractions (25 mg/kg) of hexane, dichloromethane and ethyl acetate (p < 0.05). In the electronic Von Frey by intraplantar injection of carrageenan (Cg), all fractions (25 mg/kg) were able to significantly reduce hypernociception (p < 0.05). For the determination of anti-inflammatory activity, tests were performed: Neutrophil migration to the peritoneal cavity, where all fractions (25 mg/kg) showed a significant reduction in neutrophil migration in (p < 0.05); Determination of nitrite levels, all fractions (25 mg/kg) presented a significant reduction (p < 0.05). Evaluation of vascular permeability by Evans blue, which showed a significant reduction of dye extravasation in the peritoneal fluid (p < 0.05). To determine the toxicity to Artemia saline Leach, the toxicity classifications of the fractions were active in ethanolic extract and hexane, moderate in dichloromethane and inactivated in ethyl acetate and butanol. The results allow us to consider that A. martii Benth is a promising natural source for the identification of novel bioactive compounds and therapeutic agents, as well as a promising species for use as a herbal remedy.

SIGAA | STI/SUPAC - - | Copyright © 2006-2024 - UFBA