Effect of anthracyclines and mitoxantrone on oxygen uptake and ATP intracellular concentration in rat heart slices.

The clinical use of anthracycline antibiotics is severely limited by dose-dependent cardiotoxicity. This accounts for our interest in differences on respiratory control of cardiac cells induced by two new anticancer agents epirubicin and mitoxantrone. Cellular oxygen uptake was measured for increasing drugs concentrations with a Warburg manometric apparatus and intracellular ATP by high-pressure liquid chromatography in rat heart slices incubated for 60' with anthracyclines or mitoxantrone. Epirubicin inhibits endogenous respiration by 18% versus control while doxorubicin and mitoxantrone reduce oxygen uptake by 34 and 46%, respectively. ATP intracellular concentration was significantly reduced by all anti-cancer agents but particularly by mitoxantrone 86%. These results may be related to the biochemical side effects produced by these drugs on bioenergetics and cellular respiratory control.