Abstract
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.
Highlights
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)
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, catalase, and glutathione peroxidase were observed, as opposed to the values in the controls
The increase in FRO could be determined by the nongenomic effect of aldosterone, which accumulates under conditions of prolonged mineralocorticoid receptor (MR) blockade
Summary
Жариков А.Ю.1, 2, Филинова С.О.1, Мазко О.Н.1, Макарова О.Г.1, Бобров И.П.1, Брюханов В.М.1. Изучить влияние эплеренона на активность свободнорадикального окисления и функции почек крыс при экспериментальном сахарном диабете, вызванном стрептозотоцином. Активность свободнорадикального окисления (СРО) в почках крыс, получавших эплеренон, усиливается: увеличивается концентрация тиобарбитуратреактивных продуктов в 1,5 раза (p = 0,009) и изменяется по сравнению с показателями контроля активность антиоксидантных ферментов – супероксиддисмутазы (снижается в 2,4 раза, p = 0,002), каталазы (увеличивается в 1,8, р < 0,001) и глутатионпероксидазы (увеличивается в 1,5 раза, р < 0,001). При экспериментальной ДН, вызванной у крыс введением стрептозотоцина, эплеренон оказывает нефропротекторное действие, но усиливает оксидативный стресс в почках. Нефропротекторное действие эплеренона можно связать с ослаблением геномных эффектов альдостерона, реализуемых при участии МКР. Роль свободнорадикального окисления в почках нералокортикоидных рецепторов эплеренона при экспериментальном сахарном диабете. Zharikov A.Yu. , Filinova S.O.1, Mazko O.N.1, Makarova O.G.1, Bobrov I.P.1, Bryukhanov V.M.1
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