Effects of feed-pairing and different doses of doxorubicin on mortality and electrolyte changes in the mouse heart.

Abstract

Various electrolyte changes have been documented in the hearts of different species of laboratory animals intoxicated with doxorubicin. However, it has not been determined what role the drug-induced relative nutritional lack plays in the electrolyte imbalance of this antineoplastic drug, nor to what extent the electrolyte imbalance is dose-related. A feed-pairing study performed after a single 20 mg/kg i.p. dose of doxorubicin demonstrated that relative heart weight was significantly increased in responding drug treated mice over ad libitum controls. The heart weights of feed-paired animals were also elevated to the same extent. Nutrition did not appear to have any effect on the drug-induced elevation of total ventricular calcium levels in responding animals. Although heart sodium concentrations were increased over ad libitum controls by feed restriction, they were still significantly lower than the doxorubicin-treated animals. Cardiac levels of magnesium and potassium were significantly decreased over both ad libitum and feed-paired controls. Calcium and sodium levels were increased significantly at 32 mg/kg but not at 50 or 80 mg/kg doxorubicin, while potassium and magnesium were depressed at these doses. Both the median time of death and total weight loss were inversely related to dose. It is concluded that the electrolyte disturbances are not due to the nutrition-related weight loss, and may be a proximal cause of doxorubicin-induced cardiotoxicity.