Shinozawa S, Gomita Y, Araki Y
Dept. of Hospital Pharmacy, Okayama University Medical School, Japan.
Gan To Kagaku Ryoho. 1992 Jun;19(6):805-9.
Effects of anthracycline type antitumor agents (aclarubicin, ACL; daunorubicin, DAU; doxorubicin, DOX; epirubicin, EPI; pirarubicin, PIR) on the acute toxicity to mouse, rat liver microsomal lipid peroxidation and mitochondrial functions in vitro were studied. ACL showed the least production of liver microsomal lipid peroxidation in all tested anthracyclines in the increasing order of PIR, DOX, DAU and EPI. The increase of production of lipid peroxidation induced by these drugs correlated well with the decrease in body weight of mice administered i.p. at 20 mg/kg and 50% lethal dose of these drugs. On the effect of mitochondrial function, all drugs tested decreased the oxygen uptake of state 3 and the level of respiratory control index. ACL showed the most severe inhibition of these functions in all drugs. These observations suggest that the degree of microsomal lipid peroxidation induced with the anthracycline drugs was related to the development of the drug acute toxicity.
研究了蒽环类抗肿瘤药物(阿柔比星,ACL;柔红霉素,DAU;多柔比星,DOX;表柔比星,EPI;吡柔比星,PIR)对小鼠急性毒性、大鼠肝微粒体脂质过氧化及体外线粒体功能的影响。在所有受试蒽环类药物中,按PIR、DOX、DAU和EPI的递增顺序,ACL导致的肝微粒体脂质过氧化产生量最少。这些药物诱导的脂质过氧化产生量增加与腹腔注射20mg/kg这些药物的小鼠体重减轻及50%致死剂量密切相关。关于线粒体功能的影响,所有受试药物均降低了状态3的氧摄取及呼吸控制指数水平。在所有药物中,ACL对这些功能的抑制最为严重。这些观察结果表明,蒽环类药物诱导的微粒体脂质过氧化程度与药物急性毒性的发生有关。