叔丁基羟基茴香醚对双香豆素加强阿霉素毒性的保护作用及其机制

PROTECTIVE AND ANTIOXIDATIVE EFFECTS OF 2(3) TERT BUTYL 4 HYDROXYANISOLE AGAINST DICOUMAROL ENHANCED CYTOTOXICITY CAUSED BY DOXORUBICIN IN MICE

目的：探讨叔丁基羟基茴香醚（ＢＨＡ）对双香豆素加强阿霉素毒性的保护作用及其抗氧化机制。方法：小鼠随机分为以下各组：正常对照组，双香豆素组，阿霉素组，双香豆素＋阿霉素组和ＢＨＡ＋双香豆素＋阿霉素组，每组６只。血清醌还原酶（ＱＲ）、ＡＬＴ、ＬＤＨ和ＣＫ催化活性用酶动力学方法测定，肝丙二醛（ＭＤＡ）含量按硫代巴比妥酸方法测定。结果：经双香豆素处理组血清ＱＲ催化活性显著降低。与单给阿霉素组比较，双香豆素能显著增强阿霉素所致的血清ＡＬＴ、ＬＤＨ、ＣＫ催化活性升高，肝ＭＤＡ含量也增高。ＢＨＡ具有对抗双香豆素所引起的ＱＲ催化活性降低的作用，并具有显著降低双香豆素＋阿霉素所导致的ＡＬＴ、ＬＤＨ、ＣＫ及肝ＭＤＡ含量增高的作用。结论：双香豆素具有加强阿霉素对小鼠毒性的作用，而ＢＨＡ对双香豆素加强阿霉素毒性则显示出明显保护作用。

Objective: To investigate protective and antioxidative effect of 2(3)tert butyl 4 hydroxyanisole (BHA) against dicoumarol enhanced cytotoxicity caused by doxorubicin in mice. Methods: Animals were randomly divided into 5 groups: normal control; dicoumarol; doxorubicin; dicoumarol+doxorubicin and BHA+dicoumarol+doxorubicin, 6 rats in each group. Serum quinone reductase (QR), ALT, LDH and CK activities were determined with enzyme dynamic methods. Liver malondialdehyde (MDA) content was measured by the method of thiobarbituric acid. Results: With dicoumarol pretreatment, serum QR activity was significantly decreased. In the group of dicoumarol plus doxorubicin, serum ALT, LDH, CK activities were significantly increased as compared with that of doxorubicin group alone, and liver MDA content was also increased. BHA could resist the decrease of QR activity caused by dicoumarol. BHA had caused a significantly decrease of serum ALT, LDH, CK , and liver MDA amount induced by dicoumarol plus doxorubicin. Conclusion: Dicoumarol can enhance cytotoxicity induced by doxorubicin in mice, and BHA can protect mice against cytotoxicity caused by dicoumarol plus doxorubicin. This action may relate to the increase of QR activity, and anti lipid peroxidation caused by BHA.