| Ezetimibe alone or in combination with pitavastatin prevents kidney dysfunction in 5/6 nephrectomized rats fed high-cholesterol. | |
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MedLine Citation:
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PMID: 21868047 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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We attempted to elucidate the relationship between cholesterol absorption and kidney damage by investigating the renoprotective effect of ezetimibe, a cholesterol absorption inhibitor, in 5/6 nephrectomized rats (Nx). The Nx or sham-operated rats (Sham) were fed 1% high-cholesterol diet (HC) containing ezetimibe (10 mg/[kg d]), pitavastatin (3 mg/[kg d]), or both for 8 weeks. Pathological changes, endothelial nitric oxide synthase (eNOS) messenger RNA (mRNA), and oxidative stress were assessed in the kidney. The Sham fed HC exhibited hypercholesterolemia and glomerulosclerosis with macrophage infiltration in the kidney, and ezetimibe attenuated these changes. The Nx exhibited hypercholesterolemia, increased urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), glomerulosclerosis with macrophage infiltration and interstitial fibrosis, and downregulation of eNOS mRNA. The HC increased cholesterol further and worsened the kidney damage with increased 8-OHdG. Ezetimibe attenuated the hypercholesterolemia, kidney dysfunction, and pathological changes. The beneficial effects of ezetimibe were significantly associated with reduced 8-OHdG (P < .01). Pitavastatin did not reduce cholesterol or 8-OHdG, but it did significantly suppress the kidney damage with upregulated eNOS mRNA by 2.5-fold (P < .02). The combination of ezetimibe and pitavastatin synergistically ameliorated the kidney damage. The kidney dysfunction and pathological changes were significantly associated with cholesterol, markers of cholesterol absorption (campesterol and cholestanol), and 8-OHdG (P < .001-.05). Multiple regression analysis revealed that the markers of cholesterol absorption were independently associated with the kidney damage. Ezetimibe confers renoprotective effects by inhibiting cholesterol absorption, which in turn reduces oxidative stress; and pitavastatin additively ameliorates kidney damage by increasing NO production via mechanisms independent of cholesterol reduction. |
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Authors:
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Yusaku Mori; Tsutomu Hirano |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-8-23 |
Journal Detail:
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Title: Metabolism: clinical and experimental Volume: - ISSN: 1532-8600 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-8-26 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375267 Medline TA: Metabolism Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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