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) |
|---|---|
| Pages (from-to) | 2047-2052 |
| Number of pages | 6 |
| Journal | Anticancer Research |
| Volume | 14 |
| Issue number | 5 A |
| State | Published - 1994 |
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Keywords
- Anthracycline
- Cardiotoxicity
- Doxorubicin
- Glutathione
- Heart
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Effect of doxorubicin on glutathione and glutathione-dependent enzymes in cultured rat heart cells. / Paranka, N. S.; Dorr, Robert T.
In: Anticancer Research, Vol. 14, No. 5 A, 1994, p. 2047-2052.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effect of doxorubicin on glutathione and glutathione-dependent enzymes in cultured rat heart cells
AU - Paranka, N. S.
AU - Dorr, Robert T
PY - 1994
Y1 - 1994
N2 - 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.
AB - 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.
KW - Anthracycline
KW - Cardiotoxicity
KW - Doxorubicin
KW - Glutathione
KW - Heart
UR - http://www.scopus.com/inward/record.url?scp=0028558732&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028558732&partnerID=8YFLogxK
M3 - Article
C2 - 7847848
AN - SCOPUS:0028558732
VL - 14
SP - 2047
EP - 2052
JO - Anticancer Research
JF - Anticancer Research
SN - 0250-7005
IS - 5 A
ER -