Decreased Ubiquinone Availability and Impaired Mitochondrial Cytochrome Oxidase Activity Associated With Statin Treatment
Decreased Ubiquinone Availability and Impaired Mitochondrial Cytochrome Oxidase Activity Associated With Statin Treatment
复制标题
DOI：
10.1080/15376510802305047
复制
发表时间：
2009-01-01
影响因子：
3.2
通讯作者：
Heales, Simon J. R.
中科院分区：
文献类型：
--
作者：
Duncan, Andrew J.;Hargreaves, Iain P.;Heales, Simon J. R.
为了研究线粒体电子传递链（ETC）功能障碍在3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂（他汀类药物）治疗相关的肌毒性中的潜在参与，对两名接受辛伐他汀治疗的肌病患者的ETC活性和泛醌状态进行了评估（40 mg/天）和环孢菌素（患者1）和辛伐他汀（40 mg/天）和伊曲康唑（患者2）。骨骼肌活检分析显示泛醌状态（77和132;参考范围：140-580 pmol/mg）和细胞色素氧化酶（复合物IV）活性（0.006和0.007参考范围：0.014-0.034）降低。为了评估在没有来自环孢菌素或伊曲康唑的可能药理学干扰的情况下的他汀类药物治疗，用洛伐他汀（100 M）培养原代星形胶质细胞。与对照组相比，洛伐他汀给药导致泛醌（97.9 ± 14.9;对照组：202.9 ± 18.4 pmol/mg; p 0.05）和复合物IV活性（0.008 ± 0.001;对照组：0.011 ± 0.001; p 0.05）降低。这些数据，加上病人的发现，表明他汀类药物治疗，降低泛醌状态，和复合物IV活性的损失之间可能存在关联。
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.