Effect of bile pigments on the compromised gut barrier function in a rat model of bile duct ligation.

Kangkang Zhou,Guojing Shi,Yilin Qu,Xiuhong Wang,Xinguang Yang,Mingshan Jiang,Yuanli Liu,Xiaofa Qin,Aftab A Ansari

doi:10.1371/journal.pone.0098905

Abstract

BackgroundStudies have shown that the absence of bile in the gut lumen, either by bile duct ligation or bile diversion, induces mucosal injury. However, the mechanism remains elusive. In this study, the role of bile pigments in gut barrier function was investigated in a rat model of bile duct ligation.MethodsMale Sprague Dawley (SD) rats were used in this study. After ligation of bile duct, the animals were administrated with free bilirubin, bilirubin ditaurate, or biliverdin by intragastric gavage. 1, 2, or 3 days later, the animals were sacrificed and the damage of mucosa was assessed by histological staining as well as biochemical parameters such as changes of diamine oxidase (DAO) and D-lactate (D-Lac) in the blood. Trypsin and chymotrypsin of the gut were also measured to determine how these digestive proteases may relate to the observed effects of bile pigments.ResultsBile duct ligation (BDL) caused significant increases in gut trypsin and chymotrypsin along with damage of the mucosa as demonstrated by the histological findings under microscope, the reduced expression of tight junction molecules like occludin, and significant changes in DAO and D-lac in the blood. Free bilirubin but not bilirubin ditaurate or biliverdin showed significant inhibitions on trypsin and chymotrypsin as well as alleviated changes of histological and biochemical parameters related to gut barrier disruption.ConclusionBile may protect the gut from damage through inhibiting digestive proteases like trypsin and chymotrypsin by free bilirubin.

Highlights

Multiple studies showed that the absence of bile in the gut, as seen in animals with either bile duct ligation or bile diversion, leads to mucosal injury, which was demonstrated by morphological changes such as villous atrophy, villous edema, and lacteal canal dilatation, increased intestinal permeability, and increased translocation of bacteria from the gut to other organs like the mesenteric lymph nodes, liver, and spleen [1,2,3,4,5]
As studies revealed that free bilirubin but not conjugated bilirubin or biliverdin may inhibit the activity of digestive proteases like trypsin and chymotrypsin [12,13], this may provide an explanation as to how the gut is protected against the damage by digestive proteases
Effect of Bile duct ligation (BDL) on trypsin, chymotrypsin levels We began our studies by evaluating the effect of BDL on trypsin and chymotrypsin levels, since the structural proteins of the human body may just be as vulnerable as the dietary proteins they digest

Summary

Introduction

Multiple studies showed that the absence of bile in the gut, as seen in animals with either bile duct ligation or bile diversion, leads to mucosal injury, which was demonstrated by morphological changes such as villous atrophy, villous edema, and lacteal canal dilatation, increased intestinal permeability, and increased translocation of bacteria from the gut to other organs like the mesenteric lymph nodes, liver, and spleen [1,2,3,4,5] This suggests some components in the bile may have played a critical role in maintaining gut barrier function. The role of bile pigments in gut barrier function was investigated in a rat model of bile duct ligation

Methods

Results

Conclusion