Doggrell Sheila A
Doggrell Biomedical Communications, 47 Caronia Crescent, Lynfield, Auckland, New Zealand.
Expert Opin Ther Targets. 2004 Oct;8(5):491-3. doi: 10.1517/14728222.8.5.491.
During reperfusion, the heart undergoes damage characterised by excessive production of reactive oxygen species (ROS), which may be generated by mitochondrial protein synthesis or the activity of cardiac cytochrome P450 enzymes (CYPs). Chloramphenicol inhibits both mitochondrial protein synthesis and the activity of CYPs, and in the perfused rat model of ischaemia/reperfusion, it decreased the release of creatine kinase and infarct size. This cardioprotective effect of chloramphenicol was not associated with mitochondrial protein synthesis, implicating the inhibition of CYPs in the cardioprotection. The ROS superoxide was generated by the heart in ischaemia/reperfusion, and this generation was inhibited by chloramphenicol. Inhibitors of CYP2C9 with no effect on mitochondrial protein synthesis, such as cimetidine and sulfaphenazole, are also cardioprotective in the perfused rat heart. Inhibition of CYP2C9 is a promising approach for the treatment of myocardial infarction, and should be further developed.
在再灌注期间，心脏会受到损伤，其特征是活性氧（ROS）过度产生，ROS可能由线粒体蛋白质合成或心脏细胞色素P450酶（CYPs）的活性产生。氯霉素可抑制线粒体蛋白质合成和CYPs的活性，在大鼠缺血/再灌注灌注模型中，它可减少肌酸激酶的释放和梗死面积。氯霉素的这种心脏保护作用与线粒体蛋白质合成无关，这表明CYPs的抑制在心脏保护中起作用。ROS超氧化物在缺血/再灌注过程中由心脏产生，而氯霉素可抑制这种产生。对线粒体蛋白质合成无影响的CYP2C9抑制剂，如西咪替丁和磺胺苯吡唑，在大鼠灌注心脏中也具有心脏保护作用。抑制CYP2C9是治疗心肌梗死的一种有前景的方法，应进一步开展研究。
