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


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.


CONCLUSIONS
We suggested that aldose reductase inhibitor may have preventive effect on diabetic nephropathy by reducing renal VEGF overexpression.
Sung
Joong Kyung
JK
Department of Internal Medicine, Yonsei University Wonju College of Medicine, 162 Ilsan-dong, Wonju 220-701, Korea.
Koh
Jang Hyun
JH
Lee
Mi Young
MY
Kim
Bo Hwan
BH
Nam
Soo Min
SM
Kim
Jae Hyun
JH
Yoo
Jin Hee
JH
Kim
So Hee
SH
Hong
Sun Won
SW
Lee
Eun Young
EY
Choi
Ran
R
Chung
Choon Hee
CH
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000517:prevention & control; D048289:Imidazolidines / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D048289:Imidazolidines; D042461:Vascular Endothelial Growth Factor A; C077139:fidarestat; D000449:Aldehyde Reductase; D019808:Losartan