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

Autor: Nariman Ayyad, E H Mosbach, T Hoshita, M Yoshii, B I Cohen, C D Schteingart, A. Ohshima, K Ohtani, T Mikami, K Kihira
Jazyk: angličtina
Rok vydání: 1996
Předmět:
Zdroj: Journal of Lipid Research, Vol 37, Iss 6, Pp 1189-1197 (1996)
ISSN: 0022-2275
Popis: 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.
Databáze: OpenAIRE