Document Detail


Effect of phalloidin on cholestasis, hemodynamics, and microcirculation in isolated perfused rat liver.
MedLine Citation:
PMID:  8591855     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In this study, the possible role of the hepatic microcirculation in phalloidin-induced cholestasis and hepatotoxicity was examined in isolated perfused rat livers (IPRL). Administration of a phalloidin bolus (1 mg/kg body weight) through the portal vein induced an immediate reduction of bile flow. In 16.9 minutes, bile flow was 50% lower than basal values. Portal pressure was only increased in 60 minutes after phalloidin injection and increased sharply from this time up to the end of perfusion (90 minutes). Under these conditions, phalloidin did not induce liver cell cytolysis, as assessed by aspartate transaminase (AST) and lactate dehydrogenase (LDH) release in the perfusate effluent. Under electron microscopy, hepatocytic vacuolization was mild 15 minutes after phalloidin administration but increased with time. At the end of perfusion, the hepatic architecture was markedly altered; erythrocyte accumulation was observed in both sinusoids and hepatocyte vacuoles. Evaluation by multiple indicator dilution curves showed that extravascular volume (EVV) was significantly affected by phalloidin. It was augmented in 30 minutes after phalloidin administration with values increasing gradually over time. Neither vascular nor cellular volume was altered. The hepatic swelling may be attributed to enlargement of the extravascular space of the liver. These results indicate that changes in the liver microcirculation are not the primary cause of phalloidin-induced cholestasis in the IPRL.
Authors:
C Barriault; J L Petit; M Gascon-Barré; P M Huet; I M Yousef; B Tuchweber
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  23     ISSN:  0270-9139     ISO Abbreviation:  Hepatology     Publication Date:  1996 Feb 
Date Detail:
Created Date:  1996-04-03     Completed Date:  1996-04-03     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  294-302     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Université de Montréal, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bile / physiology
Bile Acids and Salts / metabolism
Blood Pressure / drug effects
Cholestasis / chemically induced*,  pathology
Female
Hemodynamics / drug effects
Indicator Dilution Techniques
Liver / drug effects,  pathology
Liver Circulation / drug effects*
Microcirculation / drug effects
Perfusion
Phalloidine / pharmacology*
Portal System / drug effects
Rats
Rats, Sprague-Dawley
Tissue Survival / drug effects
Chemical
Reg. No./Substance:
0/Bile Acids and Salts; 17466-45-4/Phalloidine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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