The effects of pure and micellar solutions of different bile salts on mucosal morphology in rat jejunum in vivo.
The effects of pure and micellar solutions of different bile salts on mucosal morphology have been investigated in rat jejunum using a closed-loop technique; the effects of an anionic dihydroxy steroid antibiotic, fusidic acid, have also been studied. Mucosal changes were assessed by light-microscopical appearances and quantified by determining surface to volume ratios (c/1h). The unconjugated dihydroxy bile salts, chenodeoxycholate and deoxycholate (DC), produced similar and gross structural changes at concentrations of 2-5 to 5 mM, as judged by mucosal appearances, but not at 1 mM; the unconjugated trihydroxy bile salt cholate and a variety of di- and trihydroxy conjugated salts produced no changes at concentrations of 5 to 20 mM. Fusidate (5 mM) produced similar changes to 5 mM DC. Compared with control values DC (1,2-5 and 5 mM) and fusidate (5 mM) produced highly significant (P less than 0-001) reductions in c/1h ratios. DC-induced damage was completely abolished by mixed micellar solutions, whereas pure micellar solutions provided no protection. These results indicate, (i) a molecular specificity for bile salt-induced mucosal damage, and (ii) that the effects of the unconjugated dihydroxy species on mucosal structure depends not only on their intraluminal concentrations, but also on the relative concentrations of conjugated bile salts and lipids present in the lumen.
D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D003840:Deoxycholic Acid / Q000494:pharmacology; D005672:Fusidic Acid / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D007583:Jejunum / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008823:Micelles / Q000494:pharmacology; D009829:Oleic Acids / Q000494:pharmacology; D051381:Rats; D013656:Taurocholic Acid / Q000494:pharmacology
D001647:Bile Acids and Salts; D008823:Micelles; D009829:Oleic Acids; D003840:Deoxycholic Acid; D005672:Fusidic Acid; D013656:Taurocholic Acid