title: 15 alpha-hydroxylation of a bile acid analogue, sodium 3 alpha,7 alpha-dihydroxy-25,26-bishomo-5 beta-cholane-26-sulfonate in the hamster.
abstract: The metabolism of 3 alpha,7 alpha-dihydroxy-25,26-bishomo-5 beta-cholane-26-sulfonate (bishomoCDC-sul), the sulfonate analogue of bishomochenodeoxycholic acid, and its effect on biliary bile acid composition were studied during chronic administration in the hamster. After oral administration of radiolabeled bishomoCDC-sul, more than 80% of the radioactivity was excreted into the feces within 7 days, both as the unchanged sulfonate (38.5%) and two more polar metabolites (50.0% and 11.5%). The half time of the fecal excretion was 1.6 days. In gallbladder bile, the unchanged sulfonate and its major metabolite accounted for 19.1% and 19.8% of total bile acids, respectively. In another experiment, hamsters were fed bishomoCDC-sul with antibiotics to evaluate the site of biotransformation. Even when the number of intestinal microorganisms was greatly reduced, the same three metabolites were found in the feces: bishomoCDC-sul (44.0%) and the two polar metabolites (30.8% and 25.1%). The major metabolite was isolated from feces of the hamsters fed bishomoCDC-sul without antibiotics. Its chemical structure was identified by mass spectrometry and nuclear magnetic resonance spectroscopy as the 15 alpha-hydroxylated derivative, namely sodium 3 alpha,7 alpha,15 alpha-trihydroxy-25,26-bishomo-5 beta-cholane-26-sulfonate. These results indicate that after oral administration, the sulfonate analogue of bishomochenodeoxycholic acid underwent enterohepatic circulation like a natural bile acid and was transformed, in part, into the 15 alpha-hydroxylated derivative and another more polar metabolite in the liver of hamsters. There was no evidence that bishomoCDC-sul was dehydroxylated to a lithocholic acid analogue during enterohepatic cycling.
authors.affiliation: Department of Surgery, Beth Israel Medical Center, New York, NY 10003, USA.
authors.forename: T
authors.initials: T
authors.lastname: Mikami
authors.forename: A
authors.initials: A
authors.lastname: Ohshima
authors.forename: E H
authors.initials: EH
authors.lastname: Mosbach
authors.forename: B I
authors.initials: BI
authors.lastname: Cohen
authors.forename: N
authors.initials: N
authors.lastname: Ayyad
authors.forename: M
authors.initials: M
authors.lastname: Yoshii
authors.forename: K
authors.initials: K
authors.lastname: Ohtani
authors.forename: K
authors.initials: K
authors.lastname: Kihira
authors.forename: C D
authors.initials: CD
authors.lastname: Schteingart
authors.forename: T
authors.initials: T
authors.lastname: Hoshita
mesh_terms: D000818:Animals; D001646:Bile / Q000187:drug effects / Q000502:physiology*; D001647:Bile Acids and Salts / Q000378:metabolism*; D001711:Biotransformation; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D006224:Cricetinae; D006900:Hydroxylation; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015394:Molecular Structure; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013997:Time Factors
chemical_list: C093669:3,7-dihydroxy-25,26-bishomocholane-26-sulfonate; D001647:Bile Acids and Salts; D002635:Chenodeoxycholic Acid