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  • Title: Toxicity, pharmacokinetics, and cholesterol-inhibitory effect of 7-ketocholesterol.
    Author: Santillan G, Sarma JS, Pawlik G, Rackl A, Grenier A, Bing RJ.
    Journal: Atherosclerosis; 1980 Jan; 35(1):1-10. PubMed ID: 7370082.
    Abstract:
    The possible toxic effect of intravenous 7-ketocholesterol (7-KC), a steroid which has been shown to inhibit cholesterol flux in the arterial wall, was investigated in rabbits. The histology, hematology and blood chemistry were compared in 4 control animals, 3 animals receiving high doses (5.50 +/- 0.33 mg/kg/day) and 4 animals injected with lower doses 1.85 +/- 0.28 mg/kg/day) of the oxygenated sterol. Each animal received a total of 16 injections at the rate of 2 injections per day. Pharmacokinetic studies on the disappearance rate of [4-(14)C]7-KC were also carried out. Pathologic changes in the organs of animals injected with 7-KC were few. In one animal exposed to the higher concentration of 7-KC, some granulomatous angiitis in the lung was noticed. Changes in the liver were not significantly different from those observed in the control animals. Inhibition of arterial flux of cholesterol (inhibition of 55%) was noticed with high and low doses of the oxidized sterol. The disappearance curves of [14C]cholesterol in blood and plasma were characteristic of a 2-compartment model. The rate constant determining tissue uptake of 7-KC was higher than tissue efflux and there was no appreciable reflux into red cells. The results indicate that it is possible to reduce cholesterol flux in the arterial wall of rabbits without causing major toxic changes and that both red cells and tissue act as a reservoir for the oxygenated sterol.
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