Hyperlipidemic effects of adriamycin in rats

Adriamycin, an anticancer drug, caused dramatic increases in the serum lipid levels of rats fed a high-cholesterol diet. Male Lewis inbred rats were fed a basal or 1.5% cholesterol diet containing 0.5% cholic acid for 8 weeks. The rats were injected with adriamycin in doses of 1.5 mg/kg body weight, twice a week, and 6.0 mg/kg body weight, every other week. The serum lipid peroxide level gradually rose in adriamycin-treated rats, reaching a four-fold level at the end of the experiment. Cholesterol feeding, however, had a lowering effect on the lipid peroxide level. Adriamycin treatment or cholesterol feeding moderately elevated serum lipid levels, but their combination exerted a synergistic effect. In rats injected with a large dose of adriamycin and fed a high-cholesterol diet, the serum cholesterol, triglyceride and phospholipid levels strikingly increased by approx. 2000, 1500 and 1300 mg/100 ml, respectively. However, the ester ratio of cholesterol remained almost constant. Furthermore, serum GOT, GPT and ALP activities were only slightly different from the control values. Adriamycin treatment produced severe hypoalbuminemia. Ascites was also observed in rats given a large dose of adriamycin. The present findings indicate that the hyperlipidemia we observed may basically result from adriamycin-induced nephrosis and can be markedly enhanced when rats are fed a high-cholesterol diet. In spite of remarkably high levels of serum lipids and lipid peroxides, the aortic cholesterol level increased only slightly.