Tight junction permeability and liver plasma membrane fluidity in lithocholate-induced cholestasis.
The present study correlated the reversibility of bile flow (BF) impairment with biochemical and morphological changes in the liver after injection of a cholestatic dose (12 mumole/100 g body weight) of lithocholic acid (LCA). BF declined maximally at 60 min but recovered totally at 210 min after LCA treatment. During the cholestatic period, there was an increase in tight junction permeability as measured by the bile to plasma (B/P) ratio of inulin and using lanthanum as a tracer. Cholesterol content and the cholesterol/phospholipid ratio in liver plasma membranes (LPM) were augmented while the fluidity of bile canalicular membranes (BCM) was decreased at 30 and 60 min after LCA injection. These changes in cholesterol content and membrane fluidity seemed to be correlated with LCA incorporation in LPM; their reversal at 120 min preceded the recovery of BF (210 min). Some biochemical disorders were evident after LCA injection, but they did not correlate with the variation in BF. These data suggest that increased tight junction permeability and decreased BCM fluidity are important pathogenic steps in LCA-induced cholestasis.
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Department of Pharmacology, Université de Montreal, Québec, Canada.
Tuchweber
B
B
Raymond
P
P
Yousef
I M
IM
D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D002463:Cell Membrane Permeability / Q000502:physiology*; D002779:Cholestasis / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D002784:Cholesterol / Q000032:analysis; D004195:Disease Models, Animal; D007267:Injections; D007365:Intercellular Junctions / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D007444:Inulin / Q000032:analysis; D007811:Lanthanum; D008095:Lithocholic Acid / Q000008:administration & dosage / Q000009:adverse effects*; D008099:Liver / Q000166:cytology* / Q000502:physiology / Q000648:ultrastructure; D008297:Male; D008560:Membrane Fluidity / Q000502:physiology*; D010743:Phospholipids / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013223:Statistics as Topic; D013997:Time Factors
D010743:Phospholipids; D008095:Lithocholic Acid; D007811:Lanthanum; D007444:Inulin; D002784:Cholesterol