Aldose Reductase Inhibitor Ameliorates Renal Vascular Endothelial Growth Factor Expression in Streptozotocin-Induced Diabetic Rats

Abstract

PurposeThe vascular endothelial growth factor (VEGF) expression of podocyte is one of the well-known major factors in development of diabetic nephropathy. In this study, we investigated the effects of aldose reductase inhibitor, fidarestat on diabetic nephropathy, and renal VEGF expression in a type 1 diabetic rat model.Materials and MethodsTwenty four Sprague-Dawley male rats which were performed intraperitoneal injection of streptozotocin and normal six rats were divided into four groups including a normal control group, untreated diabetic control group, aldose reductase (AR) inhibitor (fidarestat, 16 mg · kg-1 · day-1) treated diabetic group, and angiotensin receptor blocker (losartan, 20 mg · kg-1 · day-1) treated diabetic group. We checked body weights and blood glucose levels monthly and measured urine albumin-creatinine ratio (ACR) at 8 and 32 weeks. We extracted the kidney to examine the renal morphology and VEGF expressions.ResultsThe ACR decreased in fidarestat and losartan treated diabetic rat groups than in untreated diabetic group (24.79 ± 11.12, 16.11 ± 9.95, and 84.85 ± 91.19, p < 0.05). The renal VEGF messenger RNA (mRNA) and protein expression were significantly decreased in the fidarestat and losartan treated diabetic rat groups than in the diabetic control group.ConclusionWe suggested that aldose reductase inhibitor may have preventive effect on diabetic nephropathy by reducing renal VEGF overexpression.