Doxorubicin induces delayed heart and liver mitochondrial depolarisation

The effect of repeated administration of doxorubicin (DOX) on heart and liver morphology, mitochondrial function and redox equilibrium was investigated in rats, contributing in explanation of delayed cardiomyopathy. Male Wistar rats were weekly intraperitoneally exposed to doxorubicin (1.5 mg/kg to achieve cumulative dose of 18 mg/kg). To assess persistence changes the heart and liver were studied 3 weeks after last drug administration. Histological examination did not reveal any significant changes in heart and liver in drug-treated animals. However, mitochondrial depolarisation was observed in both organs. These changes in the liver were accompanied by significant increasing in mitochondrial oxidised glutathione and marked decrease of reduced/oxidised glutathione ratio. No changes in cardiac and hepatic NADPH and NADH levels were found. The depolarisation of mitochondria of both studied organs after three weeks since the last injection seems to be a programmed effect of the drug. It may be assumed that this is an early physiological change leading to mitochondrial insufficiency and consequently the cardiac failure.