Hyperglycaemia-Induced Nephropathy is Prevented by Resveratrol and Pioglitazone Co-Administration in Type-2 Diabetic Male Wistar Rats

Abstract

Background: Hyperglycaemia results in oxidative stress and activation of certain pathways such as that of aldose reductase, commonly observed in the development of diabetic nephropathy. The aim of this research was to evaluate the effect of resveratrol and pioglitazone co-administration in hyperglycaemia-induced nephropathy in type-2 diabetes.

Methods: Thirty (30) adult male Wistar rats were induced with type-2 diabetes through high-fat-diet and fructose feeding for six weeks, followed by a single dose of 35 mg/kg streptozotocin (STZ) injection intraperitoneally. Rats with fasting blood glucose (FBG) levels of ≥ 200 mg/dL (20) were randomly divided into 5 groups of 4 rats each. Eight (8) other apparently healthy rats received regular diet and formed groups I and II of the experiment who received 1 ml/kg distilled water and 1 ml/kg carboxymethylcellulose (CMC) respectively, group III remained untreated, group IV, V, VI and VII received 100 mg/kg resveratrol, 5 mg/kg pioglitazone, 100 mg/kg resveratrol + 5 mg/kg pioglitazone and 1 mg/kg Lisinopril respectively. All interventions were given through oral route and lasted for six weeks post STZ injection. Rats were then fasted overnight and anaesthesized with 50 mg/kg ketamine hydrochloride and 25 mg/kg diazepam. Blood was collected via cardiac puncture in plain bottles and the right kidney of each rat was homogenized for biochemical assays. Data were analyzed and expressed as mean ± standard error of mean (SEM) using one way or repeated measure analysis of variance, followed by Tukey’s post-hoc test to compare level of significance, values of p ˂ 0.05 were considered statistically significant.

Results: There was a significant decrease (p < 0.05) in FBG levels between the co-administration and diabetic untreated groups at weeks 8, 10 and 12. Activities of antioxidant enzymes SOD, CAT and GSH in kidney homogenate increased significantly with a corresponding statistical significant decrease in MDA concentration between co-administration and diabetic untreated groups. Also, significant decreases (p< 0.05) were seen in serum levels of aldose reductase and KIM-1 in the co-administration group compared to the diabetic control.

Conclusion: The outcome of this study shows that resveratrol could potentially augment the effect of anti-diabetic drugs, in this case pioglitazone, in the prevention of diabetic nephropathy development in type-2 diabetes.