Valsartan reduces NOX4 expression and halts diabetic nephropathy in streptozotocin induced diabetic rat model

Abstract

Background: Diabetic nephropathy is the leading cause of kidney failure worldwide. NADPH oxidase 4 (NOX4) is an obvious cause for reactive oxygen species production in the kidney mainly via renin-angiotensin system. High reactive oxygen species results in kidney damage through direct effect or through activation of other pathways such as the extracellular regulated kinase (ERK) signaling pathway.Aim: The present study was constructed to investigate the effect of angiotensin II receptor blocker, valsartan, on NOX4, ERK1/2expression, and malondialdehyde level as well as their effects on the progression of diabetic nephropathy in type 1 diabetic rat model. Methods:The experimental rats were divided into three groups: group I control healthy untreated rats, group II streptozotocin-induced diabetic rats, and group III valsartan treated streptozotocin-induced diabetic rats.Results: Valsartan showed significantly decreased NOX4 and ERK1/2 mRNA, NOX4 and pERK1/2 protein concentration, and oxidative stress as evidenced by low malondialdehyde concentration in treated diabetic rats. Valsartan attenuates albuminuria, improve overall kidney function parameters, and pathological changes compared to diabetic non-treated rats.Conclusion: Valsartan treatment impedes renal damage and improve kidney function in treated diabetic nephropathy rats. The beneficial effect of valsartan was mediated through decrease oxidative stress via downregulation of NOX4 and ERK1/2 and decreased reactive oxygen species production.