Metabolism of intravenously administered 7α-hydroxycholesterol-3β-stearate in the hamster

Abstract In order to investigate the metabolic fate of serum esterified 7α-hydroxycholesterol, [4- 14 C]7α-hydroxycholesterol-3β-stearate was synthesized from labeled cholesterol and administered to bile fistula hamsters intravenously. Bile samples were collected at every 20 min for 7 h. Radioactivity was detected in bile 40 min after the beginning of the infusion of the labeled compound and 56.5 ± 5.7% (48.7–66.0%) of the administered radioactivity was recovered in bile during 7 h. The liver contained appreciable radioactivity (19.5 ± 7.6% of the administered dose) at the time of sacrifice. Only a trace amount of radioactivity was detected in urine and blood. Cumulative recovery of the radioactivity was 76.3 ± 8.6% (63.3–90.4%). Major radioactive metabolites in the bile samples were identified to be taurine- and glycine-conjugated cholic acid and chenodeoxycholic acid by radioactive thin-layer Chromatographic analysis of the bile samples before and after enzymatic hydrolysis and 3α-hydroxysteroid dehydrogenase treatment. The conversion was nearly complete and we could not detect neutral metabolites, such as the mother compound, free 7α-hydroxycholesterol and bile alcohols, as well as glucuronidated or sulfated bile acids. It is concluded that serum esterified 7α-hydroxycholesterol could be effectively taken up by the liver, hydrolyzed by cholesterol esterase and metabolized via the normal biosynthetic pathway to taurine- or glycine-conjugated primary bile acids to be excreted into bile.