Effects of adriamycin on chronic cardiotoxicity in selenium-deficient rats.
Adriamycin (doxorubicin) is an antineoplastic drug used to treat various cancers; however, its chronic use is unfortunately accompanied by cardiotoxicity. This toxicity can be reduced by antioxidant agents such as selenium, and it is particularly interesting that cancer patients are usually deficient in this trace element, which suggests that its supplementation could contribute to beneficial treatment. We have examined the effect of adriamycin on chronic cardiotoxicity in 6-week selenium deficiency in rats. Selenium-deficient rats showed a considerable reduction of selenium levels and of selenium-containing glutathione peroxidase. Cardiac lipid peroxides increased slightly in the deficient rats, whereas plasma and heart lipid peroxides increased markedly in adriamycin-treated rats. This increase was greatly accentuated in selenium deficiency. These results suggest that free radical mechanism may be contributing to adriamycin toxicity, and above all show the importance of balancing the selenium levels in adriamycin-treated subjects to limit its harmful myocardial action. A decrease in adriamycin cardiotoxicity with no concomitant decrease in its antineoplastic activity would be of considerable value by improving the therapeutic benefit of the drug.
Coudray
C
C
Laboratoire de Biochimie C, Centre Hospitalier Régional de Grenoble, France.
Mouhieddine
S
S
Richard
M J
MJ
Arnaud
J
J
De Leiris
J
J
Favier
A
A
D000818:Animals; D004317:Doxorubicin / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000097:blood; D006321:Heart / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000172:deficiency*
D004317:Doxorubicin; D005979:Glutathione Peroxidase; D012643:Selenium