Cholesterol diet increases plasma and liver concentrations of cholesterol epoxides and cholestanetriol.

Abstract

Cholesterol .alpha.-epoxide (5,6.alpha.-epoxy-5.alpha.-cholestan-3.beta.-ol [a potential carcinogen]), cholesterol .beta.-epoxide (5,6.beta.-epoxy-5.beta.-cholestan-3.beta.-ol) and cholestanetriol (5.alpha.-cholestane-3.beta.,5,6.beta.-triol) were isolated from plasma and liver of rabbits by high performance liquid chromatography and identified by gas-chromatography-mass spectrometry. The 5,6-oxygenated cholestanols in the plasma and liver of rabbits fed for 2 mo. on a diet supplemented with cholesterol were elevated to 2-5 times and 5-8 times the normal level, respectively. Among the 5,6-oxygenated steroids, the .beta.-epoxide existed at the highest level in tissues of control and cholesterol-fed rabbits. The ratios of the .beta.-epoxide to the .alpha.-epoxide were 2-3 in all the examined biological specimens just as the previously demonstrated ones in the in vitro lipid peroxidation-mediated reaction of cholesterol. The epoxidation of the cholesterol double bond in the animal may be mediated by lipid peroxidation. The elevated 5,6-oxygenated cholestanol levels on long term cholesterol feeding will be discussed in relation to a possible physiological role of cholestanetriol in regulation of tissue cholesterol levels.