Selective Mitochondrial Alterations Induced by a Single Dose of Daunorubicin or 4-Demethoxydaunorubicin in Mouse Ventricular Myocardium

Abstract

The ventricular myocardium of CD1 mice given a single high dose (LD₅₀) of daunorubicin (DNR) or its derivative, 4-demethoxydaunorubicin (4DD), was studied under the electron microscope. Severe degenerative alterations were observed, but only in the mitochondria in myocardial tissue samples taken 3 and 7 days after treatment. This suggests that mitochondrial lesions might play an important role in the pathogenesis of anthracycline myocardiopathy. Furthermore, the nucleolar segregation phenomenon, already described in experimental doxorubicin myocardiopathy, was not observed in the myocardial samples taken 1 and 3 h after DNR or 4DD injection: this fact may be interpreted, without excluding a possible DNA-mediated toxic mechanism, as the result of different kinetic behaviour of DNR and 4DD compared to doxorubicin.