Impact of physical exercise on inflammatory and apoptotic changes and redox status in rats with type 1 diabetes mellitus.
Diabetic Nephropathy. Exercise. Inflammation. Oxidative stress. Apoptosis.
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.