Hepatocyte tight-junctional permeability is increased in rat experimental colitis.
OBJECTIVE
Hepatobiliary complications occur in inflammatory bowel disease and may be caused by the translocation of intestinal toxins from portal blood into bile through leaky hepatocyte tight junctions. The role of tight junctions in the pathogenesis of hepatobiliary complications in experimental inflammatory bowel disease was investigated.


METHODS
Colitis was induced in rats by intracolonic instillation of trinitrobenzene sulfonic acid. The function of hepatocellular tight junctions was evaluated in perfused livers by measuring early (paracellular) horseradish peroxidase excretion into the bile and by electron microscopy and semiquantitative analysis of lanthanum penetration through the tight junction and into bile canaliculi. Immunofluorescent localization of cingulin and ZO-1 was used to study the structure of hepatocyte junctions.


RESULTS
Colitis was associated with increased serum bilirubin and bile acid concentrations, a 2.5-fold increase in paracellular biliary excretion of horseradish peroxidase, and a ninefold increase in lanthanum permeability. Liver histology and cingulin and ZO-1 localizations were similar to normal liver.


CONCLUSIONS
Experimental colitis is associated with hepatobiliary complications and an increased hepatocyte tight junctional permeability to horseradish peroxidase and lanthanum. Subtle alterations in tight junction function may be involved in the pathogenesis of hepatobiliary injuries in inflammatory bowel disease.
Lora
L
L
Department of Internal Medicine, University of Padova, Italy.
Mazzon
E
E
Martines
D
D
Fries
W
W
Muraca
M
M
Martin
A
A
d'Odorico
A
A
Naccarato
R
R
Citi
S
S
D000818:Animals; D000911:Antibodies, Monoclonal; D001646:Bile / Q000378:metabolism; D001648:Bile Canaliculi / Q000473:pathology; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D003106:Colon / Q000473:pathology; D019084:Fluorescent Antibody Technique, Indirect; D006735:Horseradish Peroxidase; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D007811:Lanthanum / Q000493:pharmacokinetics; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008111:Liver Function Tests; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D008854:Microscopy, Electron; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013154:Spleen / Q000473:pathology; D019108:Tight Junctions / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity; D015430:Weight Gain
D000911:Antibodies, Monoclonal; D008565:Membrane Proteins; D007811:Lanthanum; D014302:Trinitrobenzenesulfonic Acid; D006735:Horseradish Peroxidase