Hyperlipidemic Effects of Adriamycin in Rats

Abstract

Abstract-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.

The effect of doxorubicin on rats that received toxic and carcinogenic benzo(a)pyrene.

“…Values expressed as mean ± SD. a week, and it has also indicated a decrease in ALT and AP activities compared with controls [26]. AST and AP values in our study are in accordance with their results, but the increase in ALT value differs from the results of their study.…”

Lipid Deposition in the Aorta of Adjuvant Arthritic Rats with Hypercholesterolemia

“…The role of cholesterol in adjuvant arthritis has not been studied, but we observed that cholesterol feeding could lower the serum lipid peroxide level. Similar results have been obtained in a previous study (21). The relation of lipid peroxidation to adjuvant arthritis (26) and rheumatoid arthritis (27) has been reported.…”

“…However, the rat is quite resistant and cholesterol feeding alone does not produce atherosclerotic lesions. In previous studies (21,22) as well as in the present one, no significant accumulation of cholesterol in the aorta was observed in rats, despite the fact that sufficient hypercholesterolemia was achieved by cholesterol feeding alone. For the rat, vascular injury in combination with hypercholesterolemia is necessary for lipids to accumulate on the arterial wall (3,8,22,23).…”

Effect of Dexamethasone Palmitate-Low Density Lipoprotein Complex on Cholesterol Ester Accumulation in Aorta of Atherogenic Model Mice.

“…The levels of cholesterol in the aorta were determined by a fluorometric enzymatic method. 12) Briefly, 200 ml of extract and 2.5 mg of Triton X-100 were mixed and evaporated under a vacuum. The residue was suspended with 200 ml of the enzyme mixture and the suspension was incubated for 30 min at 37°C.…”