Modification of adriamycin toxicity in rats fed a high fat diet

Rats fed a diet containing a high percentage of butter, cholesterol, cholic acid and proply thiouracil (HFD) showed weight loss and developed hyperlipidemia, marked fatty infiltration of the liver, moderate elevation of SGPT, degenerative changes of the heart muscle, bradycardia, alterations of the QRS complex in the electrocardiogram, and initial hemoconcentration followed by moderate anemia. Treatment with adriamycin (18 X 1 mg/kg i.p.) resulted in significant augmentation of the cardiotoxic effects of this drug demonstrated by electrocardiographic measurements and myocardial histopathology. Adriamycin-induced atrophy of the lymphatic tissue was seen only in rats fed HFD and not in animals receiving ground chow. Adriamycin levels in the heart after single i.p. injection were higher in rats receiving HFD. This effect was present already after 10 days on HFD. At this time histopathological liver changes were present and SGPT was elevated. It is concluded that the increase in adriamycin toxicity is, at least in part, due to diminished excretion by the liver. These experimental findings are in accordance with clinical observations which have identified liver disease as one of the important risk factors for the development of adriamycin cardiomyopathy.