THE EFFECT OF COPPER DEFICIENCY ON ADRIAMYCIN TOXICITY

The effect of copper (Cu) deficiency on antioxidant status of liver and heart and its effect on adriamycin toxicity was assessed. Weanling rats were fed Cu-adequate (+Cu) and Cu-deficient (-Cu) diets for 3 weeks and then injected intraperitoneally once with saline or adriamycin (8 mg/kg). All -Cu rats had increased heart/body weight ratios compared to +Cu rats. Regardless of Cu status, adriamycin decreased body weight and increased heart cytochrome c oxidase, but had no effect on Cu,Zn-superoxide dismutase, glutathione peroxidase, the thiobarbituric acid (TBA) index or liver cytochrome c oxidase activity. -Cu, adriamycin rats had significantly decreased heart weights (0.54 + 0.02 g/kg body wt.) compared to -Cu, saline rats (0.69 +/- 0.05 g/kg body wt.). Four of 6 -Cu rats given adriamycin had abnormal EKGs, with 3 showing extrasystoles and 1 having a severe bradycardia. All +Cu rats given adriamycin had normal EKGs. Pathological changes detected with electron microscopy were most severe in -Cu rats given adriamycin.