Role of biliary phosphatidylcholine in bile acid protection and NSAID injury of the ileal mucosa in rats  Jose M. Barrios, Lenard M. Lichtenberger  Gastroenterology  Volume 118, Issue 6, Pages 1179-1186 (June 2000) DOI: 10.1016/S0016-5085(00)70371-4 Copyright © 2000 American Gastroenterological Association Terms and Conditions

Fig. 1 Schematic depiction of how biliary PC can provide protection against BS-induced intestinal injury and plays a role in the mechanism by which NSAIDs can interfere with this process. In the first case, the BS interacts with PC, forming less toxic micelles. NSAIDs secreted into the bile will in turn compete with BS for the available PC molecules, resulting in the formation of more toxic BS micelles. An alternative of this mechanism is that (1) BS attacks the hydrophobic mucosal barrier, or the intestinal membranes themselves, by detergent action; (2) PC restores these barriers by replacing the dissolved phospholipids; and (3) this protective role of PC is compromised by NSAIDs secreted into the bile as a result of intermolecular chemical association. Gastroenterology 2000 118, 1179-1186DOI: (10.1016/S0016-5085(00)70371-4) Copyright © 2000 American Gastroenterological Association Terms and Conditions

Fig. 2 The increase in the fluorescence of a buffer containing diluted bile, in response to addition of the hydrophobic dye ANS, is reduced by  ̃40% if bile is used from an animal pretreated with Indo at a dose of 25 mg/kg (○). ■, Control. Gastroenterology 2000 118, 1179-1186DOI: (10.1016/S0016-5085(00)70371-4) Copyright © 2000 American Gastroenterological Association Terms and Conditions

Fig. 3 Effect of normal bile or bile collected from rats pretreated with Indo (25 mg/kg) on the surface hydrophobicity of the ileal mucosa. The decrease in ileal surface hydrophobicity induced by exposure to bile from Indo-treated rats could be prevented by addition of PC to bile at a final concentration of 1 mg/mL. The ileal loops of control rats were instilled with an equivalent volume on saline instead of bile. *P ≤ 0.05 vs. saline-treated control values. Twenty rats per group were used in this and the experiments shown in subsequent figures, unless indicated otherwise. Gastroenterology 2000 118, 1179-1186DOI: (10.1016/S0016-5085(00)70371-4) Copyright © 2000 American Gastroenterological Association Terms and Conditions

Fig. 4 Effect of normal bile or bile collected from rats pretreated with Indo (25 mg/kg) on the Hb concentration of ileal loop fluid as an index of intestinal bleeding. The increase in intestinal bleeding induced by exposure to bile from Indo-pretreated rats could be prevented by addition of PC to bile at a final concentration of 1 mg/mL. The ileal loops of control rats were instilled with an equivalent volume of saline instead of bile. *P ≤ 0.05 vs. saline-treated control. Gastroenterology 2000 118, 1179-1186DOI: (10.1016/S0016-5085(00)70371-4) Copyright © 2000 American Gastroenterological Association Terms and Conditions

Fig. 5 Surface hydrophobicity of ileal mucosa after exposure to buffer alone or buffer containing 5 mmol/L each of the following: BS (sodium deoxycholate); Indo; and PC, alone and in combination. *P ≤ 0.05 vs. buffer-treated control values. Gastroenterology 2000 118, 1179-1186DOI: (10.1016/S0016-5085(00)70371-4) Copyright © 2000 American Gastroenterological Association Terms and Conditions

Fig. 6 Hb concentration of ileal loop fluid, as an index of GI bleeding, after exposure to buffer alone or buffer containing 5 mmol/L each of the following: BS (sodium deoxycholate); Indo; and PC, alone or in combination. *P ≤ 0.05 vs. buffer-treated control values. Gastroenterology 2000 118, 1179-1186DOI: (10.1016/S0016-5085(00)70371-4) Copyright © 2000 American Gastroenterological Association Terms and Conditions

Fig. 7 Effect of the following test agents on erythrocyte hemolysis (expressed as percentage of 100% hemolysis as caused by suspension of the cells in distilled water): BS (sodium deoxycholate), Indo, and PC. All agents were administered at a final concentration of 5 mmol/L, except for PC that was administered at both 5 and 10 mmol/L as indicated. *P ≤ 0.05 vs. buffer-treated control values. ●, Indo; ■, control. n = 20/group. Gastroenterology 2000 118, 1179-1186DOI: (10.1016/S0016-5085(00)70371-4) Copyright © 2000 American Gastroenterological Association Terms and Conditions