Hepatic 3 alpha-dehydrogenation and 7 alpha-hydroxylation of deoxycholic acid in the guinea-pig.

Abstract The metabolic fate of exogenous deoxycholate administered either intraperitoneally or intragastrically to male Hartley guinea-pigs was investigated. Two animals received a constant infusion of [24-14C]deoxycholate through an intraperitoneal catheter for 2 hr. Bile was quantitatively collected in 30 min samples during infusion and for 2 additional hours. Each bile sample was analyzed for composition and radioactivity. Five animals received for 15 days, through an intragastric catheter, 35 mg/kg/day of deoxycholate. The biliary bile acid composition was compared with that of a sham-operated control group. The studies with both animal models indicated that guinea-pigs, as the only species so far known, extensively oxidize deoxycholate to form 3-oxo,12 alpha-hydroxy-cholanic acid, which is secreted in bile mostly conjugated with glycine. In addition a small fraction (approx. 7%) of the administered deoxycholate is 7 alpha hydroxylated to form cholic acid. The metabolites being more hydrophilic than administered deoxycholate, it is suggested that guinea-pig liver counteracts the adverse increase in bile acids detergency, which follows deoxycholate administration, by converting most of the latter into less detergent compounds.