Mythili Y, Sudharsan P T, Varalakshmi P
Department of Medical Biochemistry, Dr. ALM. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, India.
Toxicology. 2005 Nov 5;215(1-2):108-14. doi: 10.1016/j.tox.2005.07.001. Epub 2005 Aug 8.
Mitochondria play a central role in heart metabolism and function. Administration of antineoplastic drug cyclophosphamide (CP) adversely affects the heart mitochondria which may result in cardiotoxicity. The present study is aimed at evaluating the role of lipoic acid (LA) in CP induced myocardial injury. Male albino rats of Wistar strain were used for the study. CP was administered as a single intraperitoneal injection (200 mg/kg BW). A decrease in the activities of TCA cycle enzymes such as succinate dehydrogenase, malate dehydrogenase and isocitrate dehydrogenase was noted in CP treated rats. Simultaneously there was a decrease in the activities of mitochondrial complexes of electron transport chain. Decrease in the activities of these enzymes suggests a loss in mitochondrial function and integrity. Ultrastuctural observations were also in agreement with the above abnormal changes. Loss of myofilaments and damage of mitochondrial cristae revealed the cytotoxic effect of CP. The supplementation of LA (25 mg/kg BW) restored the above abnormalities to near normalcy. The study brings out the importance of LA in improving the mitochondrial function in cardiac cells after CP administration.
线粒体在心脏代谢和功能中起着核心作用。抗肿瘤药物环磷酰胺(CP)的使用会对心脏线粒体产生不利影响,这可能导致心脏毒性。本研究旨在评估硫辛酸(LA)在CP诱导的心肌损伤中的作用。使用Wistar品系的雄性白化大鼠进行研究。CP通过单次腹腔注射给药(200mg/kg体重)。在CP处理的大鼠中,观察到三羧酸循环酶如琥珀酸脱氢酶、苹果酸脱氢酶和异柠檬酸脱氢酶的活性降低。同时,电子传递链的线粒体复合物活性也降低。这些酶活性的降低表明线粒体功能和完整性丧失。超微结构观察也与上述异常变化一致。肌丝的丧失和线粒体嵴的损伤揭示了CP的细胞毒性作用。补充LA(25mg/kg体重)使上述异常恢复到接近正常水平。该研究揭示了LA在CP给药后改善心脏细胞线粒体功能方面的重要性。