Abstract
This report describes the chemical synthesis of a new bile acid analogue, namely, sodium 3 alpha, 7 alpha-dihydroxy-25-homo-5 beta-cholane-25-sulfonate from homochenodeoxycholic acid. The structure of the new compound was assigned by proton magnetic resonance and infrared spectrometry. Its metabolism was studied in the hamster in comparison with sodium 3 alpha, 7 alpha-dihydroxy-24-nor-5 beta-cholane-23-sulfonate and sodium taurochenodeoxycholate. After intraduodenal administration of the 3H-labeled analogues into bile fistula hamsters, both sulfonates were absorbed from the intestine and nearly 80% of the radioactivity was secreted into bile within 8 h. Intra-ileal administration revealed that these compounds resembled taurochenodeoxycholate in that they were much more rapidly absorbed from the ileum than from the proximal small intestine: more than 85% of the radioactivity was recovered in bile within 1 h. After intravenous infusion the sulfonates were efficiently extracted by the liver at rates similar to that of sodium taurochenodeoxycholate. Chromatographic analysis of the bile showed that, regardless of the route of administration, most (> 95%) of the sulfonates were not biotransformed and they became major biliary bile acids. Sodium 3 alpha, 7 alpha-dihydroxy-25-homo-5 beta-cholane-25-sulfonate and, to a lesser extent, sodium 3 alpha, 7 alpha-dihydroxy-24-nor-5 beta-cholane-23-sulfonate induced cholestasis at infusion rates at which sodium taurochenodeoxycholate produced choleresis.
Highlights
This report describes the chemical synthesis of a new has not been entirely satisfactory
Administered CDCA and ursodeoxycholic acid (UDCA) are 7-dehydroxylated by intestinal bacteria to form lithocholic acid (LCA) [6,7,8], deoxycholate
A more recent study showed that side chain conjugation prevented 7-dehydroxylation of bile acids by Eubacterium sp
Summary
This report describes the chemical synthesis of a new has not been entirely satisfactory. Administered CDCA and UDCA are 7-dehydroxylated by intestinal bacteria to form lithocholic acid (LCA) [6,7,8], deoxycholate. After intraduodenal administration of the 3H- which is a known hepatotoxin [9,10,11] and considered by labeled analogues into bile fistula hamsters, both sulfonates were absorbed from the intestine and nearly 80% of the radioactivity was secreted into bile within 8 h. Sodium 3ar,7a-dihydroxy-25-homo-5~-cholane-25-sulfonatechain-modified bile acid analogues should be resistant to and, to a lesser extent, sodium 3a,7a-dihydroxy-24-nor-5/3cholane-23-sulfonate induced cholestasis at infusion rates at. Cholane-25-sulfonate and sodium 3a,7a-dihydroxy-24-n0~5P- Abbreviations: CDCA, chenodeoxycholic acid; UDCA, ursodeoxycholane-23-sulfonate in the hamster. J Lipid Res. 1992. 33: cholic acid; CDC-sul, 3a,7a-dihydroxy-5fl-cholane-24-sulfonatUe;DCsul, 3a,7/3-dihydroxy-5fl-cholane-24-sulfonatheo;moCDC-sul, 3a,7adihydroxy-25-homo-5~-cholane-25-sulfonaten;orCDC-sul, 3a,7a-
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