Effects of Spironolactone and Losartan on Diabetic Nephropathy in a Type 2 Diabetic Rat Model.
10.4093/dmj.2011.35.2.130
- Author:
Mi Young LEE
1
;
Myoung Sook SHIM
;
Bo Hwan KIM
;
Soon Won HONG
;
Ran CHOI
;
Eun Young LEE
;
Soo Min NAM
;
Gun Woo KIM
;
Jang Yel SHIN
;
Young Goo SHIN
;
Choon Hee CHUNG
Author Information
1. Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea. cchung@yonsei.ac.kr
- Publication Type:Original Article
- Keywords:
Diabetic nephropathy;
Losartan;
Spironolactone;
Vascular endothelial growth factor
- MeSH:
Albuminuria;
Animals;
Chemokine CCL2;
Collagen Type IV;
Diabetic Nephropathies;
Losartan;
Malondialdehyde;
Oxidative Stress;
Proteinuria;
Rats;
RNA, Messenger;
Spironolactone;
Transforming Growth Factor beta;
Transforming Growth Factors;
Vascular Endothelial Growth Factor A
- From:Diabetes & Metabolism Journal
2011;35(2):130-137
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: While there is an evidence that the anti-inflammatory properties of spironolactone can attenuate proteinuria in type 2 diabetes, its effects on vascular endothelial growth factor (VEGF) expression in diabetic nephropathy have not been clearly defined. In this study, we examined the effects of spironolactone, losartan, and a combination of these two drugs on albuminuria, renal VEGF expression, and inflammatory and oxidative stress markers in a type 2 diabetic rat model. METHODS: Thirty-three Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats were divided into four groups and treated with different medication regimens from weeks 25 to 50; OLETF diabetic controls (n=5), spironolactone-treated (n=10), losartan-treated (n=9), and combination of spironolactone- and losartan-treated (n=9). RESULTS: At week 50, the albumin-to-creatinine ratio was significantly decreased in the losartan and combination groups compared to the control OLETF group. No decrease was detected in the spironolactone group. There was a significant reduction in renal VEGF, transforming growth factor (TGF)-beta, and type IV collagen mRNA levels in the spironolactone- and combination regimen-treated groups. Twenty-four hour urine monocyte chemotactic protein-1 levels were comparable in all four groups but did show a decreasing trend in the losartan and combination regimen groups. Twenty-four hour urine malondialdehyde levels were significantly decreased in the spironolactone- and combination regimen-treated groups. CONCLUSION: These results suggest that losartan alone and a combined regimen of spironolactone and losartan could ameliorate albuninuria by reducing renal VEGF expression. Also, simultaneous treatment with spironolactone and losartan may have protective effects against diabetic nephropathy by decreasing TGF-beta and type IV collagen expression and by reducing oxidative stress in a type 2 diabetic rat model.
