The effects of pure and micellae solutions of different bile salts on mucosal morphology in rat jejunum in vivo

Abstract

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.

Studies on Hydragogue Drugs: Light and Electron Microscopic Examination of the Isolated Rat Colonic Mucosa Exposed to Deoxycholic Acid and Synthetic Surfactants

“…Furthermore, the transcellular permeability characteristics of the flattened epithelial cells may be quite another than of normal columnar enterocytes. The present study with DDS and DOC on the isolated rat colon thus confirms that these two compounds may cause morphological damage, in accordance with a previous study with DOC on this preparation (Wanitschke et al 1977a), and a number of studies on other preparations and by other technique (DDS: Nadai et al 1972Nadai et al & 1975Sugimura 1974a & b;Yonezawa 1977;DOC: Dawson et al 1960;Fry & Staffeldt 1964;Shiner 1969 Saunders et al 1975a;Keeling et al 1976;Gaginella et al 1977;Gullikson et al 1977;Yonezawa 1977;Chadwick et a!. 1979;Gordon et al 1979;Goerg 1980).…”

Effect of Bile Pigments on the Compromised Gut Barrier Function in a Rat Model of Bile Duct Ligation

“…This suggests some components in the bile may have played a critical role in maintaining gut barrier function. It has been well documented that bile acids, one of the main components in the bile, are harmful to the mucosa of the gastrointestinal tract [6]–[9]. The beneficial effect of bile on gut barrier remains to be determined.…”

Adhesion of bacteria to mucosal surfaces?an area of increasing importance in diarrhoeal disease

“…At present, our understanding of the pathophysiology of Protracted Diarrhoea is limited, but overgrowth of the upper small intestine with enterobacteria and anaerobes is a common finding, and this may be important in the pathogenesis of the diarrhoea [21]. The presence of increased numbers of bacteria in the jejunum, which is normally relatively sterile, can impair the absorptive function of the intestine by a number of mechanisms, including: (i) elaboration of bacterial enterotoxins [14]; (ii) bacterial metabolism of bile salts (deconjugation and 7a-dehydroxylation) resulting in a reduced total intraluminal concentration of bile salts and "toxic" free dihydroxy bile salts impairing the mucosal [22,23] and intraluminal phases of absorption; and (iii) damage to the glycocalyx and brush border by proteolytic and glycosidic bacterial enzymes [24,25]. At present, one can only speculate on the reasons for such bacterial overgrowth of the small intestine, but it is possible that bacteria may be able to adhere more readily to the brush borders of enterocytes lining the intestine of such infants.…”