Cardiomyopathy and other chronic toxic effects induced in rabbits by doxorubicin and possible prevention by coenzyme Q10.

Cumulative dose-dependent toxic effects, particularly cardiomyopathy, induced by doxorubicin and the possible prevention by coenzyme Q10 (CoQ10) were studied in rabbits. In rabbits given doxorubicin alone, there was considerable body weight loss, alopecia, pancytopenia, significant increase in serum creatine phosphokinase and LDH, and ECG changes characterized by tachycardia, flat and inverted T wave, the premature ventricular contractions. In rabbits given doxorubicin plus CoQ10, the only change was pancytopenia. In rabbits treated with doxorubicin alone, the most prominent histologic changes were observed in mitochondria of myocytes, and these changes were characterized by loss of outer membrane, disarrangement of cristae, and formation of numerous concentric lamellae. In addition to mitochondrial changes, there were numerous vacuolizations and extensive depositions of both electron-dense and membranous laminated bodies in the sarcoplasm and disarrangement of Z-band and filamentous changes of myofibrils. Numerous vacuolizations in the capillary endothelial cytoplasm in the myocardium were also conspicuous. On the other hand, few significant morphologic changes were seen in the nuclei of myocytes. There were few ECG and histopathologic changes in rabbits treated with both doxorubicin and CoQ10. These findings suggest that the cardiomyopathy of doxorubicin may be prevented or is at least inhibited by CoQ10. The mechanisms of both doxorubicin-induced cardiomyopathy and its prevention by CoQ10 are discussed.