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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2007-8-9
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pubmed:abstractText |
Recent studies have uncovered various pleiotrophic effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase-inhibiting drugs (statins). Several studies have identified a beneficial effect of statins on diabetic nephropathy; however, the molecular mechanisms are unclear. In this study, we show that statin ameliorates nephropathy in db/db mice, a rodent model of type 2 diabetes, via downregulation of NAD(P)H oxidase NOX4, which is a major source of oxidative stress in the kidney. Pitavastatin treatment for 2 weeks starting at 12 weeks of age significantly reduced albuminuria in the db/db mice concomitant with a reduction of urinary 8-hydroxy-2'-deoxyguanosine and 8-epi-prostaglandin F(2alpha). Immunohistochemical analysis found increased amounts of 8-hydroxy-2'-deoxyguanosine and NOX4 protein in the kidney of db/db mice. Quantitative reverse transcription-polymerase chain reaction also showed increased levels of NOX4 mRNA. Pitavastatin normalized all of these changes in the kidneys of diabetic animals. Additionally, 12-week treatment with the statin completely normalized the levels of transforming growth factor-beta1 and fibronectin mRNA as well as the mesangial expansion characteristic of diabetic nephropathy. Our study demonstrates that pitavastatin ameliorates diabetic nephropathy in db/db mice by minimizing oxidative stress by downregulating NOX4 expression. These findings may provide insight into the mechanisms of statin therapy in early stages of diabetic nephropathy.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/8-epi-prostaglandin F2alpha,
http://linkedlifedata.com/resource/pubmed/chemical/8-hydroxy-2'-deoxyguanosine,
http://linkedlifedata.com/resource/pubmed/chemical/Blood Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyguanosine,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprost,
http://linkedlifedata.com/resource/pubmed/chemical/Fibronectins,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxymethylglutaryl-CoA...,
http://linkedlifedata.com/resource/pubmed/chemical/Lipids,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Nox4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Quinolines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1,
http://linkedlifedata.com/resource/pubmed/chemical/pitavastatin
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0085-2538
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
72
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
473-80
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:17568784-Albuminuria,
pubmed-meshheading:17568784-Animals,
pubmed-meshheading:17568784-Blood Glucose,
pubmed-meshheading:17568784-Body Weight,
pubmed-meshheading:17568784-Cell Proliferation,
pubmed-meshheading:17568784-Deoxyguanosine,
pubmed-meshheading:17568784-Diabetes Mellitus, Type 2,
pubmed-meshheading:17568784-Diabetic Nephropathies,
pubmed-meshheading:17568784-Dinoprost,
pubmed-meshheading:17568784-Disease Models, Animal,
pubmed-meshheading:17568784-Down-Regulation,
pubmed-meshheading:17568784-Fibronectins,
pubmed-meshheading:17568784-Hydroxymethylglutaryl-CoA Reductase Inhibitors,
pubmed-meshheading:17568784-Lipids,
pubmed-meshheading:17568784-Male,
pubmed-meshheading:17568784-Mesangial Cells,
pubmed-meshheading:17568784-Mice,
pubmed-meshheading:17568784-NADPH Oxidase,
pubmed-meshheading:17568784-Oxidative Stress,
pubmed-meshheading:17568784-Quinolines,
pubmed-meshheading:17568784-RNA, Messenger,
pubmed-meshheading:17568784-Time Factors,
pubmed-meshheading:17568784-Transforming Growth Factor beta1
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pubmed:year |
2007
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pubmed:articleTitle |
Pitavastatin ameliorates albuminuria and renal mesangial expansion by downregulating NOX4 in db/db mice.
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pubmed:affiliation |
Department of Internal Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyusyu University, Fukuoka, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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