Banca de DEFESA: DENISAR PALMITO DOS SANTOS

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : DENISAR PALMITO DOS SANTOS
DATA : 05/12/2019
HORA: 14:00
LOCAL: Instituto Multidisciplinar em Saúde
TÍTULO:

Evaluation of new photosensitizers for photodynamic therapy in the treatment of intradermal Staphylococcus aureus infection in a murine model 

PALAVRAS-CHAVES:

Antimicrobial Photodynamic Therapy; Resveratrol; Myrciaria cauliflora; Staphylococcus aureus

PÁGINAS: 84
GRANDE ÁREA: Ciências Biológicas
ÁREA: Farmacologia
SUBÁREA: Farmacologia Geral
RESUMO:

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.

MEMBROS DA BANCA:
Interno - 1112111 - AMELIA CRISTINA MENDES DE MAGALHAES GUSMAO
Externo à Instituição - DIRCEU JOAQUIM COSTA - UESB
Externo ao Programa - 2315391 - FABRICIO FREIRE DE MELO
Interno - 1553274 - REGIANE YATSUDA
Presidente - 2497915 - ROBSON AMARO AUGUSTO DA SILVA