Role of bile salts and trypsin in the pathogenesis of experimental alkaline esophagitis.
The pathogenesis of alkaline reflux esophagitis was investigated in an experimental model by assessing individually the influence of different bile salt moieties and trypsin on esophageal mucosa. An isolated segment of rabbit esophagus was perfused at pH 7 with a solution containing the test agent under study, and the severity of mucosal damage was assessed by using as indicators of mucosal integrity transmucosal potential difference, net flux of Na+, and mucosal permeability to two neutral molecules of different sizes, 3H-H2O and 14C-erythritol. The data indicate that the secondary dihydroxy bile salt, deoxycholate, in its deconjugated form was highly injurious to esophageal mucosa; it was the only test agent that caused gross mucosal lesions during the experiment. The respective conjugated bile salt moiety, taurodeoxycholate, had a weaker effect. Also the primary dihydroxy bile salt, chenodeoxycholate, in its deconjugated form caused moderate damage to the mucosa, whereas its conjugated form, taurochenodeoxycholate, had no effect. The effect of the other three bile salts tested--cholate, taurocholate, and taurolithocholate--was negligible. Trypsin also adversely affected the mucosa, but its effect was weaker than that of deoxycholate. The results suggest that the deconjugated bile salts deoxycholate and chenodeoxycholate (which are formed following bacterial colonization of the upper gastrointestinal tract in the absence of gastric acid), the conjugated bile salt taurodeoxycholate, and the proteolytic enzyme trypsin may have significant roles in the pathogenesis of alkaline reflux esophagitis.
D000468:Alkalies; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002635:Chenodeoxycholic Acid / Q000378:metabolism; D002793:Cholic Acids / Q000378:metabolism; D003840:Deoxycholic Acid / Q000378:metabolism; D004947:Esophagus / Q000187:drug effects / Q000502:physiology*; D005764:Gastroesophageal Reflux / Q000209:etiology*; D011817:Rabbits; D013655:Taurochenodeoxycholic Acid / Q000378:metabolism; D013656:Taurocholic Acid; D013657:Taurodeoxycholic Acid / Q000378:metabolism; D013658:Taurolithocholic Acid / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism*
D000468:Alkalies; D001647:Bile Acids and Salts; D002793:Cholic Acids; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D013655:Taurochenodeoxycholic Acid; D013657:Taurodeoxycholic Acid; D013658:Taurolithocholic Acid; D013656:Taurocholic Acid; D014357:Trypsin