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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
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    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
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    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
Relationship between Menopausal Status and Metabolic Syndrome Components in Korean Women.
Jang Hyun Koh, Mi Young Lee, Soo Min Nam, Joong Kyung Sung, Pil Moon Jung, Jin Kyu Noh, Jang Yel Shin, Young Goo Shin, Choon Hee Chung
Korean Diabetes J. 2008;32(3):243-251.   Published online June 1, 2008
  • 2,450 View
  • 37 Download
  • 7 Crossref
AbstractAbstract PDF
Postmenopausal status is associated with a 60% increased risk for metabolic syndrome. It is thought to be associated with decreased estrogens and increased abdominal obesity in postmenopausal women with metabolic syndrome. The purpose of this study was to investigate the association between metabolic syndrome components and menopausal status. METHODS: A total of 1,926 women were studied and divided into three groups according to their menstrual stage (premenopausal, perimenopausal or postmenopausal). The presence of metabolic syndrome was assessed using the National Cholesterol Education Program's (NCEP) Adult Treatment Panel III criteria. RESULTS: The prevalence of metabolic syndrome was 7.1% in premenopause, 9.8% in perimenopause, and 24.2% in postmenopause. The strong correlation was noted between the metabolic syndrome score and waist circumference in postmenopause (r = 0.56, P < 0.01) and perimenopause (r = 0.60, P < 0.01). Along the menopausal transition, the risk of metabolic syndrome increased with high triglyceride after the age-adjusted (odds ratio (OR) 1.517 [95% confidence interval (CI) 1.014~2.269] in perimenopausal women and OR 1.573 [95% CI 1.025~2.414] in postmenopausal women). In addition, the prevalence of metabolic syndromeincreased in accordance with elevated alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT) levels. CONCLUSION: Triglyceride and waist circumference were important metabolic syndrome components, though ALT and GGT may also be related for predicting metabolic syndrome during the transition to menopause.


Citations to this article as recorded by  
  • Interaction between major dietary patterns and cardiorespiratory fitness on metabolic syndrome in Iranian adults: a cross-sectional study
    Hossein Shahinfar, Mahtab Ghanbari, Yahya Jalilpiran, Nastaran Payande, Mahshid Shahavandi, Nadia Babaei, Kurosh Djafarian, Cain C. C. Clark, Sakineh Shab-Bidar
    Nutrition Journal.2021;[Epub]     CrossRef
  • The Effects of Wild Ginseng Complex Pharmacopuncture Combined with Hyperthermia on Abdominal Obesity in Post-Menopause Women: Case Report
    Jeong-Eun Yoo
    Journal of Korean Medicine for Obesity Research.2016; 16(2): 133.     CrossRef
  • Factors associated with metabolic syndrome in climacteric women of southern Brazil
    A. D. Rodrigues, H. Theodoro, K. G. Mendes, V. M. Paniz, D. de Lorenzi, M. T. Anselmo Olinto
    Climacteric.2012; 16(1): 96.     CrossRef
  • Effects of Web-based Health Education on Blood Glucose and Blood Pressure Improvement in Postmenopausal Women with Impaired Fasting Blood Glucose
    Jeong-Ah Oh, Hee-Seung Kim, Min-Jeong Park, Hye-Sun Shim
    Journal of Korean Academy of Nursing.2011; 41(5): 724.     CrossRef
  • Prevalence of Metabolic Syndrome and Related Risk Factors of Elderly Residents in Andong Rural Area 2. Based on the Biochemical Measurements and Nutrient Intakes
    Hye-Sang Lee, Chong-Suk Kwon
    Journal of the Korean Society of Food Science and Nutrition.2010; 39(10): 1459.     CrossRef
  • The Association between Serum GGT Concentration and Diabetic Peripheral Polyneuropathy in Type 2 Diabetic Patients
    Ho Chan Cho
    Korean Diabetes Journal.2010; 34(2): 111.     CrossRef
  • Prevalence of Metabolic Syndrome and Related Risk Factors of Elderly Residents in Andong Rural Area 1. Based on the Anthropometric Measurements and Health Behaviors
    Hye-Sang Lee, Chong-Suk Kwon
    Journal of the Korean Society of Food Science and Nutrition.2010; 39(4): 511.     CrossRef
Alcohol Consumption, Liver Enzymes, and Prevalence of Metabolic Syndrome in Korean Adult Men.
Soo Min Nam, Ho Yeol Yu, Mi Young Lee, Jang Hyun Koh, Jang Yel Shin, Young Goo Shin, Choon Hee Chung
Korean Diabetes J. 2007;31(3):253-260.   Published online May 1, 2007
  • 2,259 View
  • 25 Download
  • 8 Crossref
AbstractAbstract PDF
Metabolic syndrome is associated with an increasing incidence of diabetes and cardiovascular disease. The relationship between the amount of alcohol consumption and the prevalence of metabolic syndrome is controversial. Our study was performed to evaluate the relationship between alcohol consumption and the prevalence of metabolic syndrome in Korean men. Also we examined the correlation of liver markers, including alanine transaminase (ALT) and gamma-glutamyl transferase (GGT) with the development of metabolic syndrome. METHODS: We enrolled 1,775 Korean men (mean age 40.0 +/- 5.8 years) who were undergone health check-ups in our hospital. Each component of metabolic syndrome was measured by using the American Association of Clinical Endocrinologists (AACE) criteria. The subjects were divided into 4 subgroups according to the amount of alcohol consumption; Group 1: no consumption, 2 (mild): those consumed less than 200 g/week, 3 (moderate): those consumed 200~399 g/week, 4 (heavy): those consumed more than 400 g/week. RESULTS: The prevalence of metabolic syndrome was 24.6%. There were significant positive correlations between the amount of alcohol consumption blood pressure, triglyceride, fasting blood glucose, GGT levels and HDL cholesterol levels. But the odds ratios for metabolic syndrome were not significantly increased in subjects with moderate alcohol consumption. The odds ratios for the metabolic syndrome significantly increased in proportion to the increasing levels of ALT and GGT. CONCLUSION: Although alcohol consumption didn't increase the prevalence of metabolic syndrome, the amount of alcohol consumption had significant positive correlation with components of metabolic syndrome in Korean men, and elevated ALT and GGT levels could strongly associate with the prevalence of metabolic syndrome.


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  • Resting Heart Rate, QTc Interval, and Laboratory Variables in Relation to Risk Factors of Metabolic Syndrome in Korean Adult Male
    Chul-Gyu Kim, Sun Kyung Cha
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  • An Investigation on the Metabolic Syndromes and Health-Related Risk Factors among Male Workers
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  • The Association of Metabolic Syndrome and Serum γ-Glutamyl Transpeptidase: A 4-Year Cohort Study of 3,698 Korean Male Workers
    Jung Hyun Lee, Mi Hyang Um, Yoo Kyoung Park
    Clinical Nutrition Research.2013; 2(1): 67.     CrossRef
  • The incidence of metabolic syndrome and its risk factor in who under went medical check-up in a health promotion center
    Hae-Kyung Cheon, Tae-Yong Lee, In-Sun Kwon
    Journal of the Korea Academia-Industrial cooperation Society.2012; 13(3): 1186.     CrossRef
  • Metabolic Syndrome and Serum Alanine Aminotransferase Levels in Korean Adults : The Third Korea National Health and Nutrition Examination Survey (KNHANES III), 2005.
    Mi Ah Han, So Yeon Ryu, Jong Park, Myung Geun Kang, Ki Soon Kim
    Korean Journal of Epidemiology.2008; 30(1): 25.     CrossRef

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