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Glutathione protects cardiac and skeletal muscle from cyclophosphamide-induced toxicity.

Publication ,  Journal Article
Friedman, HS; Colvin, OM; Aisaka, K; Popp, J; Bossen, EH; Reimer, KA; Powell, JB; Hilton, J; Gross, SS; Levi, R
Published in: Cancer Res
April 15, 1990

Administration of cyclophosphamide at a dose which is lethal to 10% of control athymic nude mice resulted in sudden death within 3 h in all mice that had been pretreated with the glutathione synthesis inhibitor L-buthionine-SR-sulfoximine. In Fischer 344 rats pretreated with L-buthionine-SR-sulfoximine, the cyclophosphamide dose producing 100% acute toxicity was lowered from 500-150 mg/kg; cardiac monitoring revealed ventricular fibrillation to be the cause of death. These and additional studies reported demonstrate that cytoplasmic glutathione is an important protectant against the cardiac and skeletal muscle toxicity of cyclophosphamide and indicate that such toxicity may be substantially increased by glutathione depletion. Since diet and many drugs (including cyclophosphamide itself) are known to affect glutathione levels, the present studies suggest that cardiac and skeletal muscle glutathione content is likely to be a clinically significant determinant of the frequency and severity of the adverse drug interactions and systemic toxicity sometimes observed during cyclophosphamide therapy.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

April 15, 1990

Volume

50

Issue

8

Start / End Page

2455 / 2462

Location

United States

Related Subject Headings

  • Rats, Inbred F344
  • Rats
  • Phosphoramide Mustards
  • Oncology & Carcinogenesis
  • Myocardium
  • Muscles
  • Mice, Nude
  • Mice
  • Methionine Sulfoximine
  • Male
 

Citation

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Friedman, H. S., Colvin, O. M., Aisaka, K., Popp, J., Bossen, E. H., Reimer, K. A., … Levi, R. (1990). Glutathione protects cardiac and skeletal muscle from cyclophosphamide-induced toxicity. Cancer Res, 50(8), 2455–2462.
Friedman, H. S., O. M. Colvin, K. Aisaka, J. Popp, E. H. Bossen, K. A. Reimer, J. B. Powell, J. Hilton, S. S. Gross, and R. Levi. “Glutathione protects cardiac and skeletal muscle from cyclophosphamide-induced toxicity.Cancer Res 50, no. 8 (April 15, 1990): 2455–62.
Friedman HS, Colvin OM, Aisaka K, Popp J, Bossen EH, Reimer KA, et al. Glutathione protects cardiac and skeletal muscle from cyclophosphamide-induced toxicity. Cancer Res. 1990 Apr 15;50(8):2455–62.
Friedman, H. S., et al. “Glutathione protects cardiac and skeletal muscle from cyclophosphamide-induced toxicity.Cancer Res, vol. 50, no. 8, Apr. 1990, pp. 2455–62.
Friedman HS, Colvin OM, Aisaka K, Popp J, Bossen EH, Reimer KA, Powell JB, Hilton J, Gross SS, Levi R. Glutathione protects cardiac and skeletal muscle from cyclophosphamide-induced toxicity. Cancer Res. 1990 Apr 15;50(8):2455–2462.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

April 15, 1990

Volume

50

Issue

8

Start / End Page

2455 / 2462

Location

United States

Related Subject Headings

  • Rats, Inbred F344
  • Rats
  • Phosphoramide Mustards
  • Oncology & Carcinogenesis
  • Myocardium
  • Muscles
  • Mice, Nude
  • Mice
  • Methionine Sulfoximine
  • Male