Linked Life Data

2707734

Source:http://linkedlifedata.com/resource/pubmed/id/2707734

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1989-5-30
pubmed:abstractText
Isaxonine and several other drugs transformed by cytochrome P-450 into reactive metabolites apparently lead to immunoallergic hepatitis in man. Protein epitopes modified by the covalent binding of the metabolites have been proposed as possible targets for the immune response. The purpose of this work was to determine whether covalently bound metabolites are indeed present on hepatocyte plasma membrane proteins. In a first series of experiments, rats were killed 15 or 60 min after administration of [2-14C]isaxonine (0.2 mmol.kg-1 i.p.), and various fractions were prepared from isolated hepatocytes; microsomal contamination of the plasma membrane fraction was 1.2% or less. At 60 min, the amount of isaxonine metabolite covalently bound per mg of protein was similar in plasma membranes (0.42 nmole metabolite.mg protein-1) and in microsomes (0.38); both values were decreased by about 70% in rats pretreated with piperonyl butoxide, an inhibitor of cytochrome P-450. At 15 min, however, covalent binding to plasma membrane proteins (0.06 nmole metabolite.mg protein-1) was only half of that to microsomal proteins (0.12). In a second series of experiments, [2-14C] isaxonine (0.1 mM) was incubated with NADPH, hepatic microsomes and plasma membranes. The reactive isaxonine metabolite became bound extensively to microsomal proteins, but not to plasma membrane proteins. These results show that administration of isaxonine leads to the presence of isaxonine adducts on the proteins of the hepatocyte plasma membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0270-9139
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
675-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Presence of covalently bound metabolites on rat hepatocyte plasma membrane proteins after administration of isaxonine, a drug leading to immunoallergic hepatitis in man.
pubmed:affiliation
Unité de Recherches de Physiopathologie Hépatique, INSERM U 24, Hôpital Beaujon, Clichy, France.
pubmed:publicationType
Journal Article