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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
Diabetes Metab J. 2011;35(2):130-137.   Published online April 30, 2011
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  • 65 Download
  • 15 Crossref
AbstractAbstract PDFPubReader   

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.


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).


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.


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.


Citations to this article as recorded by  
  • Tetrahydrocurcumin Add‐On therapy to losartan in a rat model of diabetic nephropathy decreases blood pressure and markers of kidney injury
    Mahyar Khazaeli, Ane C. F. Nunes, Yitong Zhao, Mahziar Khazaali, John Prudente, Nosratola D. Vaziri, Bhupinder Singh, Wei Ling Lau
    Pharmacology Research & Perspectives.2023;[Epub]     CrossRef
  • Type 2 Diabetes Mellitus: Pathogenic Features and Experimental Models in Rodents
    Inessa G. Gvazava, M. V. Karimova, A. V. Vasiliev, E. A. Vorotelyak
    Acta Naturae.2022; 14(3): 57.     CrossRef
  • Role of mineralocorticoid receptor antagonists in kidney diseases
    Vishal Patel, Amit Joharapurkar, Mukul Jain
    Drug Development Research.2021; 82(3): 341.     CrossRef
  • Multi-strain probiotic supplement attenuates streptozotocin-induced type-2 diabetes by reducing inflammation and β-cell death in rats
    Pei-Shan Hsieh, Hsieh-Hsun Ho, Shu Ping Tsao, Shih-Hung Hsieh, Wen-Yang Lin, Jui-Fen Chen, Yi-Wei Kuo, Shin-Yu Tsai, Hui-Yu Huang, Michael W. Greene
    PLOS ONE.2021; 16(6): e0251646.     CrossRef
  • Ocular surface complications in diabetes: The interrelationship between insulin and enkephalin
    Indira Purushothaman, Ian S. Zagon, Joseph W. Sassani, Patricia J. McLaughlin
    Biochemical Pharmacology.2021; 192: 114712.     CrossRef
  • Mineralocorticoid Receptor Antagonists in Diabetic Kidney Disease
    Daiji Kawanami, Yuichi Takashi, Yoshimi Muta, Naoki Oda, Dai Nagata, Hiroyuki Takahashi, Makito Tanabe
    Frontiers in Pharmacology.2021;[Epub]     CrossRef
  • Effects of single and dual RAAS blockade therapy on progressive kidney disease transition to CKD in rats
    Devesh Aggarwal, Gaaminepreet Singh
    Naunyn-Schmiedeberg's Archives of Pharmacology.2020; 393(4): 615.     CrossRef
  • Bioactive Agent Discovery from the Natural Compounds for the Treatment of Type 2 Diabetes Rat Model
    Shih-Chun Yang, Ching-Yun Hsu, Wei-Ling Chou, Jia-You Fang, Shih-Yi Chuang
    Molecules.2020; 25(23): 5713.     CrossRef
  • Losartan improves renal function and pathology in obese ZSF-1 rats
    Zhi Su, Deborah Widomski, Arthur Nikkel, Laura Leys, Marian Namovic, Diana Donnelly-Roberts, Murali Gopalakrishnan, Steve McGaraughty
    Journal of Basic and Clinical Physiology and Pharmacology.2018; 29(3): 281.     CrossRef
  • Analyzing polymeric nanofibrous scaffold performances in diabetic animal models for translational chronic wound healing research
    Nowsheen Goonoo, Archana Bhaw-Luximon
    Nanotechnology Reviews.2017; 6(6): 583.     CrossRef
  • Stimulatory effect of insulin on renal proximal tubule sodium transport is preserved in type 2 diabetes with nephropathy
    Motonobu Nakamura, Nobuhiko Satoh, Masashi Suzuki, Haruki Kume, Yukio Homma, George Seki, Shoko Horita
    Biochemical and Biophysical Research Communications.2015; 461(1): 154.     CrossRef
  • Combination therapy with spironolactone and candesartan protects against streptozotocin-induced diabetic nephropathy in rats
    Amal Hofni, Mohamed A. El-Moselhy, Ashraf Taye, Mohamed M. Khalifa
    European Journal of Pharmacology.2014; 744: 173.     CrossRef
  • Renal Protective Role of Xiexin Decoction with Multiple Active Ingredients Involves Inhibition of Inflammation through Downregulation of the Nuclear Factor-κB Pathway in Diabetic Rats
    Jia-sheng Wu, Rong Shi, Jie Zhong, Xiong Lu, Bing-liang Ma, Tian-ming Wang, Bin Zan, Yue-ming Ma, Neng-neng Cheng, Fu-rong Qiu
    Evidence-Based Complementary and Alternative Medicine.2013; 2013: 1.     CrossRef
  • The use of animal models in diabetes research
    Aileen JF King
    British Journal of Pharmacology.2012; 166(3): 877.     CrossRef
  • Effect of Eplerenone, a Selective Aldosterone Blocker, on the Development of Diabetic Nephropathy in Type 2 Diabetic Rats
    Jae Hee Ahn, Ho Cheol Hong, Myong Jin Cho, Yoon Jung Kim, Hae Yoon Choi, Chai Ryoung Eun, Sae Jeong Yang, Hye Jin Yoo, Hee Young Kim, Ji A Seo, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi, Nan Hee Kim
    Diabetes & Metabolism Journal.2012; 36(2): 128.     CrossRef
Protective Effects of Lithospermic Acid B on Diabetic Nephropathy in OLETF Rats Comparing with Amlodipine and Losartan.
Eun Seok Kang, Beom Seok Kim, Chul Hoon Kim, Gi Ho Seo, Seung Jin Han, Sung Wan Chun, Kyu Yeon Hur, Chul Woo Ahn, Hunjoo Ha, Mankil Jung, Bong Soo Cha, Hyun Chul Lee
Korean Diabetes J. 2008;32(1):10-20.   Published online February 1, 2008
  • 2,493 View
  • 19 Download
  • 1 Crossref
AbstractAbstract PDF
Lithospermic acid B (LAB), an active component isolated from Salvia miltiorrhizae, has been reported to have renoprotective effects in type 1 and type 2 diabetic animal models. We examined the effects of LAB on the prevention of diabetic nephropathy compared with amlodipine, a calcium channel blocker, and losartan, an angiotensin receptor blocker, in Otsuka Long-Evans-Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. METHODS: LAB (20 mg/kg), amlodipine (10 mg/kg), or losartan (10 mg/kg) was given orally once daily to 10-week-old male OLETF rats for 28 weeks. RESULTS: None of LAB, losartan, and amlodipine exhibited effects on blood glucose levels. Treatment with amlodipine or losartan resulted in similar reductions in blood pressure; however, LAB was less effective in lowering blood pressure. Albuminuria was markedly suppressed by losartan and LAB, but not by amlodipine. LAB treatment decreased levels of renal lipid peroxidation, monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-beta1 (TGF-beta1). CONCLUSION: These results suggest that LAB has beneficial effects on the diabetic nephropathy in OLETF rats by decreasing oxidative stress and inflammation as potent as losartan.


Citations to this article as recorded by  
  • An Overview on Naturally Occurring Phytoconstituent: Lithospermic Acid
    Bhupesh Chander Semwal, Amjad Hussain, Sonia Singh
    The Natural Products Journal.2024;[Epub]     CrossRef

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