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

Yonsei Med J. 2010 May;51(3):385-91. doi: 10.3349/ymj.2010.51.3.385.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Angiotensin Receptor Antagonists
  • Antihypertensive Agents
  • Imidazolidines
  • Vascular Endothelial Growth Factor A
  • fidarestat
  • Aldehyde Reductase
  • Losartan