Aldose reductase inhibitor ameliorates renal vascular endothelial growth factor expression in streptozotocin-induced diabetic rats.

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Authors: Joong Kyung Sung ; Jang Hyun Koh ; Mi Young Lee ; Bo Hwan Kim ; Soo Min Nam ; Jae Hyun Kim ; Jin Hee Yoo ; So Hee Kim ; Sun Won Hong ; Eun Young Lee ; Ran Choi ; Choon Hee Chung

MeSH: Aldehyde Reductase/antagonists & inhibitors* ; Angiotensin Receptor Antagonists* ; Animals ; Antihypertensive Agents/therapeutic use ; Diabetes Mellitus, Experimental/drug therapy* ; Diabetes Mellitus, Experimental/metabolism* ; Diabetic Nephropathies/prevention & control ; Imidazolidines/therapeutic use* ; Kidney/drug effects* ; Kidney/metabolism* ; Kidney/pathology ; Losartan/therapeutic use ; Male ; Rats ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A

Keywords: Aldose reductase inhibitor ; vascular endothelial growth factor ; albumin creatinine ratio ; diabetic nephropathy

Abstract: PURPOSE: The 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 METHODS: Twenty 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.

RESULTS: The 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.

CONCLUSION: We suggested that aldose reductase inhibitor may have preventive effect on diabetic nephropathy by reducing renal VEGF overexpression.