title: Low-Dose Lipopolysaccharide Causes Biliary Injury by Blood Biliary Barrier Impairment in a Rat Hepatic Ischemia/Reperfusion Model.
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.
authors.affiliation: School of Medicine, The University of Queensland, Brisbane, Australia.|Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, Australia.|PA Research Foundation, Princess Alexandra Hospital, Brisbane, Australia.|Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: Janske
authors.initials: J
authors.lastname: Reiling
authors.affiliation: School of Medicine, The University of Queensland, Brisbane, Australia.|Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, Australia.
authors.forename: Kim R
authors.initials: KR
authors.lastname: Bridle
authors.affiliation: Departments of Pathology.|Molecular Genetics, Cardiovascular Research Institute Maastricht, the Netherlands.|Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Marion
authors.initials: M
authors.lastname: Gijbels
authors.affiliation: Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands.
authors.forename: Frank G
authors.initials: FG
authors.lastname: Schaap
authors.affiliation: School of Medicine, The University of Queensland, Brisbane, Australia.|Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, Australia.
authors.forename: Lesley
authors.initials: L
authors.lastname: Jaskowski
authors.affiliation: School of Medicine, The University of Queensland, Brisbane, Australia.|Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, Australia.
authors.forename: Nishreen
authors.initials: N
authors.lastname: Santrampurwala
authors.affiliation: School of Medicine, The University of Queensland, Brisbane, Australia.|Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, Australia.
authors.forename: Laurence J
authors.initials: LJ
authors.lastname: Britton
authors.affiliation: Envoi Specialist Pathologists, Brisbane, Australia.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Campbell
authors.affiliation: Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands.|Department of HPB Surgery and Liver Transplantation, Institute for Liver and Digestive Health, Royal Free Hospitals, University College London, London, UK.
authors.forename: Steven W M
authors.initials: SW
authors.lastname: Olde Damink
authors.affiliation: School of Medicine, The University of Queensland, Brisbane, Australia.|Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, Australia.
authors.forename: Darrell H G
authors.initials: DH
authors.lastname: Crawford
authors.affiliation: Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands.|Department of Surgery, RWTH Universitätsklinikum Aachen, Aachen, Germany.
authors.forename: Cornelius H C
authors.initials: CH
authors.lastname: Dejong
authors.affiliation: School of Medicine, The University of Queensland, Brisbane, Australia.|Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, Australia.|PA Research Foundation, Princess Alexandra Hospital, Brisbane, Australia.|Queensland Liver Transplant Service, Princess Alexandra Hospital, Brisbane, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Fawcett
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000097:blood; D001652:Bile Ducts / Q000098:blood supply / Q000473:pathology*; D001663:Bilirubin / Q000097:blood; D062445:Claudin-1 / Q000378:metabolism; D062465:Claudin-3 / Q000378:metabolism; D004195:Disease Models, Animal; D008070:Lipopolysaccharides / Q000633:toxicity*; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion / Q000009:adverse effects; D015427:Reperfusion Injury / Q000150:complications*; D052096:Warm Ischemia / Q000009:adverse effects*
chemical_list: D001647:Bile Acids and Salts; D062445:Claudin-1; D062465:Claudin-3; C568114:Cldn1 protein, rat; C568124:Cldn3 protein, rat; D008070:Lipopolysaccharides; D000410:Alanine Transaminase; D001663:Bilirubin