The role of free radical oxidation in the kidneys in the nephroprotective action of eplerenone, a mineralocorticoid receptor antagonist, in experimental diabetes mellitus

 Aim. To study the effect of eplerenone on the activity of free radical oxidation and renal function in rats with experimental diabetes mellitus induced by streptozotocin.

Materials and methods. Experiments were carried out on 36 male Wistar rats. Diabetes mellitus (DM) was simulated by a single intraperitoneal injection of streptozotocin at a dose of 65 mg/kg. Eplerenone was injected into the stomach at a dose of 50 mg/kg.

Results. It was found that eplerenone in experimental diabetic nephropathy (DN) significantly attenuated proteinuria: the concentration of protein in the urine became 4 times lower than in untreated DN (p < 0.001). In the kidneys, eplerenone therapy normalized the structure and function of renal glomeruli and restored the podocyte number, which was reduced by 37.8% in the DN model. Free radical oxidation (FRO) in the kidneys of rats treated with eplerenone increased – the concentration of thiobarbituric acid reactive substances rose by 1.5 times (p = 0.009), and changes in the activity of antioxidant enzymes, such as superoxide dismutase (a decrease by 2.4 times, p = 0.002), catalase (an increase by 1.8 times, р < 0,001), and glutathione peroxidase (an increase by 1.5 times, р < 0.001) were observed, as opposed to the values in the controls.

Conclusion. In streptozotocin-induced experimental diabetic nephropathy in rats, eplerenone had a nephroprotective effect, but increased oxidative stress in the kidneys. The increase in FRO could be determined by the nongenomic effect of aldosterone, which accumulates under conditions of prolonged mineralocorticoid receptor (MR) blockade. The nephroprotective effect of eplerenone can be associated with the weakening of the genomic effects of aldosterone, realized with the participation of MR. 

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