Effects of doxorubicin on mouse heart catalase

The behaviour of heart and liver catalase was studied 4 days after the administration of different doxorubicin doses to CD 1 mice. The antiblastic increased the specific activity of the heart enzyme with a clear dose-response relationship (+27% after 5 mg/kg i.p.; +61% after 7 mg/kg; + 108% after 10 mg/kg; + 147% after 15 mg/kg). This did not occur in the liver where, on the contrary, a significant reduction of catalase (-31%) was noticed after the highest dose. Analyses by gel filtration excluded the possibility that doxorubicin induces major changes in the molecular properties of heart catalase. In vivo experiments with aminotriazole, which blocks catalase irreversibly, indicated that doxorubicin stimulates the synthesis of cardiac catalase. These findings are discussed with reference to the possible mechanisms of anthracycline cardiotoxicity. The catalase elevation could represent a reaction by the heart to free radicals generated by doxorubicin.