The effect of chronic administration of doxorubicin on the rat cardiac and hepatic glutathione redox system

The effect of chronic administration of doxorubicin on the rat heart and liver glutathione redox system was studied. Rats were administered doxorubicin, 1 mg/kg, ip., three times a week, on Monday, Wednesday and Friday. One week was skipped and then the cycle repeated for a total of one, four, seven or ten doses. It was determined that treatment in this manner had no effect on rat heart glutathione, glutathione peroxidase or glucose-6- phosphate dehydrogenase, at any of the time intervals tested. However, hepatic glutathione content was found to be moderately increased after the fourth dose and glucose-6-phosphate dehydrogenase activity was found to be markedly increased after the seventh and tenth doses. Hepatic glutathione peroxidase was not affected. These results suggest that the cardiac glutathione redox system does not respond to chronic administration of doxorubicin. In contrast, the hepatic systems do respond, which may explain the apparent resistance of this organ to doxorubicin toxicity.