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Training associated with N-acetylcysteine and modulation of purinergic receptors in the progression of experimental diabetic nephropathy

Abstract

Diabetic nephropathy stands out as the main determinant of end-stage renal disease and oxidative stress (increase in reactive oxygen species - ROS) and endothelial dysfunction are some of its major aggravating factors. Recent studies in our Laboratory showed that the diabetic rats had reduced body weight, increased levels of creatinine and urea excretion and plasma TBARS as compared with respective controls; these effects were attenuated with exercises. N-acetylcysteine (NAC), an antioxidant, reduces ROS and attenuates the endothelial dysfunction; similar effects have been observed in training protocols. This study will evaluate the oxidative stress and activation of the purinergic receptors in uninephrectomized (UNx) rats, subjected to training and/or supplementation with NAC. Male Wistar rats with 8 weeks of age will be all UNx. Diabetes Mellitus (DM) will be induced with streptozotocin (60mg/kg, iv) in half of these animals, and the others will receive the vehicle (CTL). Half of both groups will be trained (CTL+EX and DM+EX) and the others will be considered sedentary (CTL+SE and DM+SE). NAC (600mg/L) will be given in drinking water in half of each group: CTL+SE+NAC, CTL+EX+NAC, DM+SE+NAC and DM+EX+NAC. The exercise training will consist of treadmill running, at 16m/min for 60min/day, 5 days/week for 8 weeks. Before and after the exercise period, blood samples and 24 hours urine will be collected. Data will be expressed as mean ±SEM, with one way ANOVA with Student-Newman-Keuls post-hoc analysis, with significance of P<0.05. (AU)