Abstract
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.
Original language | English (US) |
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Pages (from-to) | 2047-2052 |
Number of pages | 6 |
Journal | Anticancer research |
Volume | 14 |
Issue number | 5 A |
State | Published - Dec 1 1994 |
Keywords
- Anthracycline
- Cardiotoxicity
- Doxorubicin
- Glutathione
- Heart
ASJC Scopus subject areas
- Oncology
- Cancer Research