Ascorbic acid and adriamycin toxicity.
Adriamycin (ADR) is effective against a wide range of human neoplasms. However, its clinical use is compromised by serious cardiac toxicity, possibly through induction of peroxidation in cardiac lipids. Ascorbic acid, a potent antioxidant, was examined for effect in reducing ADR toxicity in mice and guinea pigs. Ascorbic acid had no effect on the antitumor activity of ADR in mice inoculated with leukemia L1210 or Ehrlich ascites carcinoma, but it significantly prolonged the life of animals treated with ADR. ADR elevated lipid peroxide levels in mouse heart, and ascorbic acid prevented the elevation. The significant prevention of ADR-induced cardiomyopathy in guinea pigs by ascorbic acid was proved by electron microscopy. Ascorbic acid and the derivatives may delay general toxicity of ADR and also prevent the cardiac toxicity. The results also suggest the clinical efficacy of the combined treatment of ADR and ascorbic acid or the derivatives.
Shimpo
K
K
Institute for Comprehensive Medical Science, School of Medicine, Fujita Health University, Aichi, Japan.
Nagatsu
T
T
Yamada
K
K
Sato
T
T
Niimi
H
H
Shamoto
M
M
Takeuchi
T
T
Umezawa
H
H
Fujita
K
K
D000818:Animals; D001205:Ascorbic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D009202:Cardiomyopathies / Q000139:chemically induced / Q000473:pathology; D004317:Doxorubicin / Q000009:adverse effects*; D006168:Guinea Pigs; D007942:Leukemia, Experimental / Q000188:drug therapy; D008054:Lipid Peroxides / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009206:Myocardium / Q000648:ultrastructure; D009368:Neoplasm Transplantation
D008054:Lipid Peroxides; D004317:Doxorubicin; C061185:2-O-octadecylascorbic acid; D001205:Ascorbic Acid; C031226:6-O-palmitoylascorbic acid