Low-dose lipopolysaccharide causes biliary injury by blood biliary barrier impairment in a rat hepatic ischemia/reperfusion model

Reiling, Janske, Bridle, Kim R., Gijbels, Marion, Schaap, Frank G., Jaskowski, Lesley, Santrampurwala, Nishreen, Britton, Laurence J., Campbell, Catherine M., Olde Damink, Steven W. M., Crawford, Darrell H. G., Dejong, Cornelius H. C. and Fawcett, Jonathan (2017) Low-dose lipopolysaccharide causes biliary injury by blood biliary barrier impairment in a rat hepatic ischemia/reperfusion model. Liver Transplantation, 23 2: 194-206. doi:10.1002/lt.24681


Author Reiling, Janske
Bridle, Kim R.
Gijbels, Marion
Schaap, Frank G.
Jaskowski, Lesley
Santrampurwala, Nishreen
Britton, Laurence J.
Campbell, Catherine M.
Olde Damink, Steven W. M.
Crawford, Darrell H. G.
Dejong, Cornelius H. C.
Fawcett, Jonathan
Title Low-dose lipopolysaccharide causes biliary injury by blood biliary barrier impairment in a rat hepatic ischemia/reperfusion model
Journal name Liver Transplantation   Check publisher's open access policy
ISSN 1527-6473
1527-6465
Publication date 2017-02-01
Year available 2017
Sub-type Article (original research)
DOI 10.1002/lt.24681
Open Access Status Not yet assessed
Volume 23
Issue 2
Start page 194
End page 206
Total pages 13
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Language eng
Abstract This study explored whether bacterial endotoxins, in the form of lipopolysaccharides (LPS), could have an injurious effect on the biliary tract in conjunction with ischemia. A total of 64 rats were randomly assigned to 4 groups: sham operation (sham group), 1 mg/kg LPS intraperitoneal (LPS group), hepatic ischemia/reperfusion (IR; IR group), and IR combined with LPS (IR+LPS group). Following 1 or 6 hours of reperfusion, serum liver tests, bile duct histology, immunofluorescence microscopy (zonula occludens-1 [ZO-1]), bile composition (bile salts, phospholipids, lactate dehydrogenase), hepatic gene expression (bile salt transporters and inflammatory mediators), as well as serum and biliary cytokine concentrations were quantified and compared between the study groups. In addition, the integrity of the blood biliary barrier (BBB) was assayed in vivo using horseradish peroxidase (HRP). LPS administration induced severe small bile duct injury following 6 hours of reperfusion. Furthermore, total bile salts and bilirubin concentrations in serum were increased in the LPS groups compared with sham controls (LPS, + 3.3-fold and +1.9-fold; IR+LPS, + 3.8-fold and +1.7-fold, respectively). The BBB was impaired in the LPS groups as evidenced by elevated levels of HRP in bile (+4.9-fold), and decreased expression of claudin 1 (–6.7-fold) and claudin 3 (–3.6-fold). LPS was found to be a potent inducer of small bile duct injury following hepatic ischemia and 6 hours of reperfusion. This injury was associated with increased permeability of the BBB and impaired hepatic bile salt clearance. Liver Transplantation 23 194–206 2017 AASLD.
Keyword Gastroenterology & Hepatology
Surgery
Transplantation
Gastroenterology & Hepatology
Surgery
Transplantation
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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