TY - JOUR
T1 - Low-Dose Lipopolysaccharide Causes Biliary Injury by Blood Biliary Barrier Impairment in a Rat Hepatic Ischemia/Reperfusion Model
AU - Reiling, Janske
AU - Bridle, Kim R.
AU - Gijbels, Marion
AU - Schaap, Frank G.
AU - Jaskowski, Lesley
AU - Santrampurwala, Nishreen
AU - Britton, Laurence J.
AU - Campbell, Catherine M.
AU - Damink, Steven W. M. Olde
AU - Crawford, Darrell H. G.
AU - Dejong, Cornelius H. C.
AU - Fawcett, Jonathan
PY - 2017/2
Y1 - 2017/2
N2 - 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 11.9-fold; IR+LPS, 13.8-fold and +11.7-fold, respectively). The BBB was impaired in the LPS groups as evidenced by elevated levels of HRPin bile (+14.9-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.
AB - 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 11.9-fold; IR+LPS, 13.8-fold and +11.7-fold, respectively). The BBB was impaired in the LPS groups as evidenced by elevated levels of HRPin bile (+14.9-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.
KW - ORTHOTOPIC LIVER-TRANSPLANTATION
KW - BILE-DUCT INJURY
KW - BACTERIAL TRANSLOCATION
KW - SCLEROSING CHOLANGITIS
KW - ISCHEMIA-REPERFUSION
KW - HEMORRHAGIC-SHOCK
KW - ENDOTOXIN LEVELS
KW - DONOR LIVERS
KW - ALPHA
KW - CHOLANGIOCYTES
U2 - 10.1002/lt.24681
DO - 10.1002/lt.24681
M3 - Article
C2 - 27880979
SN - 1527-6465
VL - 23
SP - 194
EP - 206
JO - Liver Transplantation
JF - Liver Transplantation
IS - 2
ER -