| Metabolism of antipyrine in vivo in two rat models of liver cirrhosis. Its relationship to intrinsic clearance in vitro and microsomal membrane lipid composition. | |
| | |
MedLine Citation:
|
PMID: 8216358 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Antipyrine metabolism depends on at least three isoenzymes of cytochrome P450 forming the main metabolites 3-OH-, 4-OH- and norantipyrine. We investigated to what extent antipyrine clearance and metabolite formation are impaired in two models of liver cirrhosis in the rat, namely micronodular cirrhosis induced by chronic exposure to phenobarbital/CCl4 and biliary cirrhosis induced by bile duct ligation. Salivary antipyrine clearance was decreased to a similar extent in cirrhosis induced by CCl4 and bile duct ligation (-35%). Clearance for production of 3-OH-antipyrine was decreased in both models, while 4-hydroxylation was maintained. Metabolic clearance of both 3-OH-antipyrine and 4-OH-antipyrine in vivo correlated with their clearance in vitro (r = 0.658 and r = 0.583) but not with that of norantipyrine. The microsomal cholesterol content was increased by 16% and 90% in CCl4 and bile duct-ligated cirrhotic rats (P < 0.001), respectively. Membrane fluidity, expressed as the ratio of phospholipids to cholesterol, correlated with the in vivo clearance for production of norantipyrine (r = 0.841) but not of 3-OH- or 4-OH-antipyrine, while clearance in vitro was not related to altered lipid composition. Our results demonstrate that the cytochrome P450 isoenzymes responsible for the different pathways of antipyrine metabolism are affected to different extents by cirrhosis. Alterations in intrinsic clearance explain only part of the loss of hepatocellular function. Altered lipid composition contributes to this loss of function but other factors, among them loss of hepatocytes and changes in microcirculation, could be more important determinants of the decrease in xenobiotic metabolism in cirrhosis. |
| | |
Authors:
|
J T Buters; T Zysset; J Reichen |
Related Documents
:
|
416438 - Stimulation of bilirubin catabolism in jaundiced gunn rats by an induced of microsomal ... 17297428 - Genistein decreases liver fibrosis and cholestasis induced by prolonged biliary obstruc... 19356088 - Effects of cyclosporine a and itraconazole on permeability, biliary excretion and pharm... 8206448 - Biliary excretion of the mycotoxin fumonisin b1 in rats. 3943558 - Rapid isolation of rat liver secondary lysosomes--autophagic vacuoles--following chloro... 9020548 - The time course of ultrastructural changes in the secretory components of pancreatic ac... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Biochemical pharmacology Volume: 46 ISSN: 0006-2952 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 1993 Sep |
Date Detail:
|
Created Date: 1993-11-01 Completed Date: 1993-11-01 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: ENGLAND |
Other Details:
|
Languages: eng Pagination: 983-91 Citation Subset: IM |
Affiliation:
|
Department of Clinical Pharmacology, University of Berne, Switzerland. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Antipyrine / metabolism*, pharmacokinetics, urine Bile Acids and Salts / blood Breath Tests Carbon Tetrachloride Lipids / analysis Liver Cirrhosis, Biliary / metabolism*, pathology Liver Cirrhosis, Experimental / metabolism*, pathology Male Membrane Fluidity Microsomes, Liver / metabolism, ultrastructure Models, Biological Organ Size Phenobarbital Rats Rats, Sprague-Dawley Saliva / metabolism |
| Chemical | |
Reg. No./Substance:
|
0/Bile Acids and Salts; 0/Lipids; 50-06-6/Phenobarbital; 56-23-5/Carbon Tetrachloride; 60-80-0/Antipyrine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: In vitro oxidation of pyrazinamide and allopurinol by rat liver aldehyde oxidase.
Next Document: A novel pathway for formation of thiol metabolites and cysteine conjugates from cysteine conjugate s...