Effect of pitavastatin on type 2 diabetes mellitus nephropathy in KK-A(y)/Ta mice.

Effect of pitavastatin on type 2 diabetes mellitus nephropathy in KK-A(y)/Ta mice. Research Abstract Details 

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Effect of pitavastatin on type 2 diabetes mellitus nephropathy in KK-A(y)/Ta mice. Abstract Text:

It is generally considered that 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) have renoprotective effects via a pathway independent of their cholesterol-lowering cascade. In the kidneys of diabetic nephropathy, monomeric endothelial nitric oxide synthase (eNOS) is thought to be overexpressed; and its dimerization is suppressed. In the present study, we investigated the expression of eNOS and oxidative stress in type 2 diabetes mellitus KK-A(y)/Ta mice treated with pitavastatin, one of the statins. The KK-A(y)/Ta mice were divided into 3 groups and given pitavastatin intraperitoneally starting at 8 weeks of age for 8 weeks: pitavastatin 3 mg/(kg d) (n = 5), pitavastatin 10 mg/(kg d) (n = 5), and a control group (n = 10). The urinary albumin-creatinine ratio (ACR), urinary 8-hydroxy-2'-deoxyguanosine, body weight, fasting blood glucose, hemoglobin A(1c), total cholesterol, and triglyceride were measured; and the intraperitoneal glucose tolerance test was performed. The eNOS, nitrotyrosine, and p47 phox were evaluated by immunohistochemical analyses and/or Western blot analyses. Guanosine triphosphate cyclohydrolase 1 messenger RNA expression in the kidneys was evaluated using a real-time polymerase chain reaction assay. Pitavastatin improved the levels of urinary ACR and 8-hydroxy-2'-deoxyguanosine, intraperitoneal glucose tolerance test, and hemoglobin A(1c). Protein levels of monomeric eNOS, nitrotyrosine, and p47 phox in the kidneys were decreased in the pitavastatin-treated groups. Guanosine triphosphate cyclohydrolase 1 messenger RNA expression was significantly increased in the pitavastatin groups. There were no significant changes in body weight, levels of fasting blood glucose, serum total cholesterol, triglyceride, and blood pressure among all groups. Pitavastatin improved urinary ACR apparently because of suppression of eNOS uncoupling and its antioxidant effect in the kidneys of KK-A(y)/Ta mice.

Effect of pitavastatin on type 2 diabetes mellitus nephropathy in KK-A(y)/Ta mice. Publishing Authors By Initials

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Effect of pitavastatin on type 2 diabetes mellitus nephropathy in KK-A(y)/Ta mice. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Metabolism: clinical and experimental

VOLUME: 57

Page Numbers: 691-7

Journal Abbreviation: Metab. Clin. Exp.

ISSN: 0026-0495

DAY: 29

MONTH: May

YEAR: 2008

Effect of pitavastatin on type 2 diabetes mellitus nephropathy in KK-A(y)/Ta mice. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Effect of pitavastatin on type 2 diabetes mellitus nephropathy in KK-A(y)/Ta mice.

AFFILIATION: Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan.

Country: United States

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MEDLINETA: Metabolism

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