Effect of adriamycin on the metabolism of heart slices

Incubation of Adriamycin (ADR) with either microsomal fractions or human erythrocytes results in the generation of reactive oxygen compounds (ROC). In mice administration of ADR causes lipid peroxidation and soluble sulfhydryl depletion of cardiac tissue. This study determined the effect of ADR on the metabolism of rat heart slices in vitro. Resting heart slices had a high rate of Krebs cycle activity as indicated by the oxidation of ¹⁴C-6-glucose and a low rate of hexose monophosphate shunt activity (HMPS) as indicated by the oxidation of ¹⁴C-1-glucose compared to ¹⁴C-6-glucose. Adriamycin (100μg/ml) stimulated HMPS activity 2 fold but did not change Krebs cycle activity. The HMPS pathway of heart slices incubated under anaerobic conditions was not stimulated by ADR. Unexpectedly, heart slices incubated with ¹⁴C-formate and catalase had a high baseline oxidation of this substrate which was not augmented by ADR. These studies indicate that ADR stimulates the HMPS activity of rat heart without altering Krebs cycle activity. The observation that the stimulation is dependent on oxygen suggests the generation of ROC. Resting heart slices have a high baseline production of H₂O₂ which does not appear to be associated with stimulation of the HMPS pathway. This observation suggests that H₂O₂ is not degraded adequately by the HMPS pathway in cardiac tissue. These studies are consistent with the concept that ROC may be important in the cardiac toxicity of ADR related in part to a sensitivity of cardiac tissue to oxidant injury.