Effects of resveratrol and metformin treatments on anti – apoptotic proteins in kidney tissue in rats with nephrotic syndrome

Nephrotic syndrome (NS) is an important cause of childhood renal failure, but its pathogenesis has not been fully elucidated yet. Apoptosis appears to be an important mechanism of injury in NS. However, there is not enough information about the kidney tissue levels of anti-apoptotic proteins associated with apotosis in NS and the treatment methods that may be effective on these proteins. In our study, serum and kidney tissue levels of pro-apoptotic caspase-3 and anti-apoptotic proteins XIAP and survivin were measured and their responses to potential anti-apoptotic resveratrol and metformin treatments were investigated in adriamycin induced experimental NS model. The rats that administered adriamycin intraperitoneally were randomly divided into 3 groups. The rats in group 1 (n=11) did not receive any treatment. At the end of the second week following adriamycin administration for four weeks rats in Group 2 (n=8) treated with resveratrol; group 3 (n=7) were also given metformin therapy. Rats in group 4 (n=10) were followed as control group. Caspase-3, XIAP and survivin levels were measured by ELISA method in serum and kidney tissue lysates obtained at the end of the sixth week. Pathological evaluation was made by scoring to determine the glomerular, tubular and interstitial damages in the kidney tissues of the rats in the experimental groups. Renal tissue levels of survivin, XIAP, and caspase-3 were similar in untreated rats to the control group. Renal tissue survivin values of rats treated with resveratrol and metformin showed a statistically significant decrease compared to the untreated group. Serum survivin and XIAP levels of rats with nephrotic syndrome were found to be statistically significantly higher than the control group. Serum caspase-3 levels were lower than the control group and statistically significantly lower. Resveratrol and metformin treatments equally increased serum caspase-3 levels compared to untreated rats, making them similar to the control group. Serum total cholesterol and triglyceride levels were not affected by resveratrol and metformin treatments. Ischemic collapse in kidney tissue of untreated rats was not observed in any nephrotic rats with treated resveratrol and metformin. It was determined that glomerular damage was significantly reduced with resveratrol and metformin therapy. Interstitial injury also decreased statistically significantly with metformin treatment. Resveratrol and metformin treatments did not reduce tubular damage. It was found that there was a statistically significant decrease in proteinuria levels at the end of the experiment in nephrotic rats with resveratrol and metformin treatments compared to 4th week. It was determined that proteinuria continued to increase in untreated rats. Our results show that resveratrol and metformin could be used as supportive therapies alongside currently used immunosuppressive drugs. Larger clinical and laboratory studies are needed to demonstrate the efficacy of metformin and resveratrol treatments in patients with nephrotic syndrome.