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Association between risk of myopathy and cholesterol-lowering effect: A comparison of all statins

机译：肌病风险与降胆固醇作用之间的关联：所有他汀类药物的比较

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In the present study, we examined the mechanisms underlying the cytotoxicity of pitavastatin, a new statin, and we compared the in vitro potencies of muscle cytotoxicity using a prototypic embryonal rhabdomyosarcoma cell line (RD cells), a typical side effect of statins and compared the cholesterol-lowering effects of statins using Hep G2 hepatoma cells. Pitavastatin reduced the number of viable cells and caused caspase-9 and -3/7 activation in a time- and concentration-dependent manner. The comparison of cytotoxities of statins showed that statins significantly reduced cell viability and markedly enhanced activity of caspase-3/7 in concentration-dependent manner. On the other hand, the effects of hydrophilic statins, pravastatin, rosuvastatin were very weak. The rank order of cytotoxicity was cerivastatin > sinavastatin acid> fluvastatin > atorvastatin > lovastatin acid > pitavastatin rosuvastatin, pravastatin. Statin-induced cytotoxicity is associated with these partition coefficients. On the other hand, the cholesterol-lowering effect of statins did not correlate with these partition coefficients and cytotoxicity. Thus, it is necessary to consider the association between risk of myopathy and cholesterol-lowering effect of a statin for precise use of statins. (c) 2008 Elsevier Inc. All rights reserved.
机译：在本研究中，我们研究了一种新的他汀类药物匹伐他汀的细胞毒性的潜在机制，并使用原型胚胎横纹肌肉瘤细胞系（RD细胞），他汀类药物的典型副作用，比较了肌肉细胞毒性的体外效力，并比较了使用Hep G2肝癌细胞对他汀类药物的胆固醇降低作用。匹伐他汀减少了活细胞的数量，并以时间和浓度依赖性的方式引起了caspase-9和-3/7的活化。他汀类药物的细胞毒性的比较表明，他汀类药物以浓度依赖的方式显着降低了细胞活力并显着增强了caspase-3 / 7的活性。另一方面，亲水性他汀类药物，普伐他汀，瑞舒伐他汀的作用非常弱。细胞毒性的排序是西立伐他汀>西那伐他汀酸>氟伐他汀>阿托伐他汀>洛伐他汀酸>匹伐他汀罗苏伐他汀，普伐他汀。他汀诱导的细胞毒性与这些分配系数有关。另一方面，他汀类药物的降胆固醇作用与这些分配系数和细胞毒性无关。因此，为了精确使用他汀类药物，有必要考虑肌病风险与他汀类药物的降胆固醇作用之间的关联。 （c）2008 Elsevier Inc.保留所有权利。

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