Effects of spironolactone and losartan on diabetic nephropathy in a type 2 diabetic rat model

Mi Young Lee, 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

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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)-β, 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-β and type IV collagen expression and by reducing oxidative stress in a type 2 diabetic rat model.

Original languageEnglish
Pages (from-to)130-137
Number of pages8
JournalDiabetes and Metabolism Journal
Volume35
Issue number2
DOIs
Publication statusPublished - 2011 Apr 1

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Spironolactone
Losartan
Diabetic Nephropathies
Vascular Endothelial Growth Factor A
Transforming Growth Factors
Kidney
Oxidative Stress
Collagen
Inbred OLETF Rats
Urine
Albuminuria
Chemokine CCL2
Drug Combinations
Malondialdehyde
Proteinuria
Type 2 Diabetes Mellitus
Albumins
Creatinine
Anti-Inflammatory Agents
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism

Cite this

Lee, Mi Young ; Shim, Myoung Sook ; Kim, Bo Hwan ; Hong, Soon Won ; Choi, Ran ; Lee, Eun Young ; Nam, Soo Min ; Kim, Gun Woo ; Shin, Jang Yel ; Shin, Young Goo ; Chung, Choon Hee. / Effects of spironolactone and losartan on diabetic nephropathy in a type 2 diabetic rat model. In: Diabetes and Metabolism Journal. 2011 ; Vol. 35, No. 2. pp. 130-137.
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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)-β, 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-β and type IV collagen expression and by reducing oxidative stress in a type 2 diabetic rat model.",
author = "Lee, {Mi Young} and Shim, {Myoung Sook} and Kim, {Bo Hwan} and Hong, {Soon Won} and Ran Choi and Lee, {Eun Young} and Nam, {Soo Min} and Kim, {Gun Woo} and Shin, {Jang Yel} and Shin, {Young Goo} and Chung, {Choon Hee}",
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Lee, MY, Shim, MS, Kim, BH, Hong, SW, Choi, R, Lee, EY, Nam, SM, Kim, GW, Shin, JY, Shin, YG & Chung, CH 2011, 'Effects of spironolactone and losartan on diabetic nephropathy in a type 2 diabetic rat model', Diabetes and Metabolism Journal, vol. 35, no. 2, pp. 130-137. https://doi.org/10.4093/dmj.2011.35.2.130

Effects of spironolactone and losartan on diabetic nephropathy in a type 2 diabetic rat model. / Lee, Mi Young; Shim, Myoung Sook; Kim, Bo Hwan; Hong, Soon Won; Choi, Ran; Lee, Eun Young; Nam, Soo Min; Kim, Gun Woo; Shin, Jang Yel; Shin, Young Goo; Chung, Choon Hee.

In: Diabetes and Metabolism Journal, Vol. 35, No. 2, 01.04.2011, p. 130-137.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of spironolactone and losartan on diabetic nephropathy in a type 2 diabetic rat model

AU - Lee, Mi Young

AU - Shim, Myoung Sook

AU - Kim, Bo Hwan

AU - Hong, Soon Won

AU - Choi, Ran

AU - Lee, Eun Young

AU - Nam, Soo Min

AU - Kim, Gun Woo

AU - Shin, Jang Yel

AU - Shin, Young Goo

AU - Chung, Choon Hee

PY - 2011/4/1

Y1 - 2011/4/1

N2 - 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)-β, 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-β and type IV collagen expression and by reducing oxidative stress in a type 2 diabetic rat model.

AB - 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)-β, 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-β and type IV collagen expression and by reducing oxidative stress in a type 2 diabetic rat model.

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