Decreased Ubiquinone Availability and Impaired Mitochondrial Cytochrome Oxidase Activity Associated With Statin Treatment

被引：26

作者：

Duncan, Andrew J. ^{[1
]}

Hargreaves, Iain P. ^{[1
,2
]}

Damian, Maxwell S. ^{[3
]}

Land, John M. ^{[1
,2
]}

Heales, Simon J. R. ^{[1
,2
]}

机构：

[1] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 1BG, England

[2] Natl Hosp Neurol & Neurosurg, Neuromet Unit, London WC1N 3BG, England

[3] Univ Hosp Leicester, Dept Neurol, Leicester, Leics, England

来源：

TOXICOLOGY MECHANISMS AND METHODS | 2009年 / 19卷 / 01期

关键词：

Ubiquinone; Electron transport chain; Statin; Cytochrome oxidase; COA REDUCTASE INHIBITORS; HIGH-DOSE SIMVASTATIN; COENZYME-Q LEVELS; NITRIC-OXIDE; SKELETAL-MUSCLE; RESPIRATORY-CHAIN; NEUROBLASTOMA-CELLS; SYNTHASE EXPRESSION; PRIMARY CULTURE; P-GLYCOPROTEIN;

D O I：

10.1080/15376510802305047

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

In order to investigate the potential involvement of mitochondrial electron transport chain (ETC) dysfunction in myotoxicity associated with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) treatment, assessment was made of ETC activity and ubiquinone status in two patients experiencing myopathy following treatment with simvastatin (40 mg/day) and cyclosporin (patient 1) and simvastatin (40 mg/day) and itraconazole (patient 2). Analysis of skeletal muscle biopsies revealed a decreased ubiquinone status (77 and 132; reference range: 140-580 pmol/mg) and cytochrome oxidase (complex IV) activity (0.006 and 0.007 reference range: 0.014-0.034). To assess statin treatment in the absence of possible pharmacological interference from cyclosporin or itraconazole, primary astrocytes were cultured with lovastatin (100 M). Lovastatin treatment resulted in a decrease in ubiquinone (97.9 14.9; control: 202.9 18.4 pmol/mg; p 0.05), and complex IV activity (0.008 0.001; control: 0.011 0.001; p 0.05) relative to control. These data, coupled with the patient findings, indicate a possible association between statin treatment, decreased ubiquinone status, and loss of complex IV activity.

引用

页码：44 / 50

页数：7

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