Paranka N S, Dorr R T
Cell Pathways, Inc., Denver, Colorado 80290.
Anticancer Res. 1994 Sep-Oct;14(5A):2047-52.
The effect of doxorubicin (DOX) on heart cell glutathione (GSH)-based enzyme systems was investigated in a rat heart myocyte model. Cellular levels of GSH decreased commensurate with viability following exposure to DOX or to the unrelated alkaloidal cardiotoxin emetine. GSH depletion by L-buthionine sulfoximine (L-BSO) did not alter myocyte viability nor doxorubicin (DOX) dose-response. The nitrosourea carmustine (BCNU), which impairs GSH reductase activity, also did not alter DOX cardiotoxicity. Doxorubicin significantly increased glutathione-S-transferase (GST) activity in a time-dependent fashion. In contrast, selenium-dependent glutathione peroxidase activity was reduced by 50%. These findings demonstrate that lowered GSH or GSH reductase levels do not enhance DOX cardiotoxicity in vitro and suggest that DOX may be a substrate for GST.
在大鼠心肌细胞模型中研究了阿霉素（DOX）对基于心脏细胞谷胱甘肽（GSH）的酶系统的影响。暴露于DOX或无关的生物碱心脏毒素吐根碱后，细胞内GSH水平随活力下降而相应降低。L-丁硫氨酸亚砜胺（L-BSO）消耗GSH并未改变心肌细胞活力，也未改变阿霉素（DOX）的剂量反应。损害GSH还原酶活性的亚硝基脲卡莫司汀（BCNU）也未改变DOX的心脏毒性。阿霉素以时间依赖性方式显著增加谷胱甘肽-S-转移酶（GST）活性。相比之下，硒依赖性谷胱甘肽过氧化物酶活性降低了50%。这些发现表明，降低的GSH或GSH还原酶水平在体外不会增强DOX的心脏毒性，并提示DOX可能是GST的底物。
