Failure of cholestyramine to prevent bile salt injury to mouse gastric mucosa.
Bile salts have been implicated in the pathogenesis of gastritis and gastric ulcer. Because the bile salt binding agent cholestyramine has been suggested as a possible therapy for gastric ulcer, we studied the effects of cholestyramine, in the form of Questran, on bile salt-induced injury to mouse gastric mucosa. Solutions of taurocholate or of glycochenodeoxycholate, with or without added Questran, were instilled into the stomachs of fasted mice at pH 1, 3, 5, and 7. Taurocholate damaged the mucosa only at pH 1, whereas glycochenodeoxycholate caused injury at pH 1 and 3. Questran failed to prevent mucosal damage by either bile salt. The ineffectiveness of cholestyramine to prevent injury may be due to the nonionized fraction of bile salts at pH's below their pKa's which will not be sequestered by the anion exchange resin. This phenomenon may help explain the insignificant effect of Qestran treatment in promoting healing of gastric ulcers in a previous clinical trial.
D000818:Animals; D001647:Bile Acids and Salts / Q000009:adverse effects*; D002635:Chenodeoxycholic Acid / Q000009:adverse effects / Q000031:analogs & derivatives; D002792:Cholestyramine Resin / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005753:Gastric Mucosa / Q000473:pathology*; D005756:Gastritis / Q000473:pathology / Q000517:prevention & control*; D006851:Hydrochloric Acid / Q000009:adverse effects; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D013276:Stomach Ulcer / Q000473:pathology / Q000517:prevention & control*; D013656:Taurocholic Acid / Q000009:adverse effects
D001647:Bile Acids and Salts; D002635:Chenodeoxycholic Acid; D002792:Cholestyramine Resin; D013656:Taurocholic Acid; D006851:Hydrochloric Acid