Linked Life Data

4024668

Source:http://linkedlifedata.com/resource/pubmed/id/4024668

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1985-9-25
pubmed:abstractText
The formation of ligand complexes between hepatic microsomal cytochrome P-450 and safrole, isosafrole and other methylenedioxyphenyl compounds was studied in vivo and in vitro in rats pretreated with either phenobarbital or 3-methylcholanthrene. Both the phenobarbital-induced cytochrome P-450 and the 3-methylcholanthrene-induced cytochrome P-448 metabolically convert safrole, isosafrole, and those metabolites possessing an intact methylenedioxy group, to reactive metabolites which then interact with the cytochromes to form ligand complexes. Formation of these ligand complexes was accompanied by loss of mixed-function oxidase activities, and dissociation of the complexes with the type I substrate biphenyl restored activities. Safrole and, to a lesser extent, 1'-hydroxysafrole formed complexes in vivo when administered to phenobarbital-pretreated rats; none was obtained with epoxysafrole. However, when administered to 3-methylcholanthrene-pretreated animals all three compounds formed complexes, safrole being the least effective. Epoxysafrole and 1'-hydroxysafrole administered to phenobarbital-pretreated rats resulted in slight inhibition of the type I binding of safrole to liver microsomal P-450 in vitro; in contrast, with 3-methylcholanthrene-pretreated animals marked competitive inhibition was observed. This study shows that oxidation of the allyl chain of safrole analogues enhances their affinity for cytochrome P-448, but not for cytochrome P-450, and further demonstrates that these cytochromes possess distinctly different binding sites.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0049-8254
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
333-42
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1985
pubmed:articleTitle
Ligand-complex formation between cytochromes P-450 and P-448 and methylenedioxyphenyl compounds.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't