Angiotoxicity and arteriosclerosis due to contaminants of USP-grade cholesterol.
Impurities were concentrated from several lots of cholesterol by recrystallizing cholesterol from methanol solution, retaining the mother liquor, and evaporating the residuum to dryness under vacuum. This concentrate contained the products of spontaneous oxidation of cholesterol and other contaminants from the original source. The concentrate increased the frequency of dead aortic smooth muscle cells and induced focal intimal edema in the rabbit 24 hours after gavage at 250 mg/kg. New or old cholesterol was similarly angiotoxic, the old more so than the new. Cholesterol purified via dibromination induced an increase in aggregate debris in 24 hours at 250 mg/kg but no increase in degenerated cells. The concentrate administered at a total dose of 1 gm/kg/seven weeks induced intimal, fibrous lesions without foam cells or hypercholesterolemia. Purified cholesterol at the same dose produced no effect.
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000648:ultrastructure; D001161:Arteriosclerosis / Q000139:chemically induced*; D001808:Blood Vessels / Q000187:drug effects*; D002784:Cholesterol / Q000494:pharmacology / Q000592:standards*; D004340:Drug Contamination; D009130:Muscle, Smooth / Q000187:drug effects / Q000648:ultrastructure; D011817:Rabbits
D002784:Cholesterol