Effect of doxorubicin on glutathione and glutathione-dependent enzymes in cultured rat heart cells
Paranka, N.S.; Dorr, R.T.
Anticancer Research 14(5a): 2047-2052
1994
ISSN/ISBN: 0250-7005 PMID: 7847848 Document Number: 432493
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.