Effects of adriamycin on chronic cardiotoxicity in selenium-deficient rats

Abstract

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.

Protecting against anthracycline‐induced myocardial damage: a review of the most promising strategies

“…Cancer patients have slightly lower mean selenium levels than do healthy controls (Faber et al , 1995). Several studies have found that selenium deficiency enhances doxorubicin cardiotoxicity in rats (Coudray et al , 1992; Matsuda et al , 1997). In other animal studies, selenium supplementation limited anthracycline‐induced cardiotoxicity by increasing the activity of cardiac mitochondrial GSHPx, reducing the myocardial malondialdehyde content, and abolishing the structural changes of sarcomeres induced by doxorubicin (Boucher et al , 1995).…”

Free Radicals and Reactive Oxygen Species

“…Of these enzymes, xanthine oxidase is by far the most studied and has been used extensively as a source of superoxide and hydrogen peroxide in vitro. However, a number of studies also indicate that xanthine oxidase is not an important source of free radicals in vivo (Coudray et al, 1992;Rashba et al, 1990;Werns et al, 1991). In vivo, the dehydrogenase form predominates, although conversion to the oxidase form (either by thiol oxidation or proteolysis) occurs under some pathologic situations.…”

Impact of dietary selenium intake on cardiac health: Experimental approaches and human studies

“…In this context, two main groups of studies have been carried out, a first one with those related to selenium deficiency in rats and a second one with the effects of selenium supplementation in several experimental models []. Most authors [], but not all [], reported that selenium as well as GPx‐1 deficiencies lead to an increased doxorubicin cardiotoxicity in rats. These studies mainly concluded that lipid peroxidation, or free radical generation, was involved in the toxic effects occurring in the selenium deficient rats, which through several direct or indirect mechanisms (DNA oxidative damage, mitochondrial alterations, etc.)…”