Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2004-7-2
pubmed:abstractText
We evaluated the role of specific isoforms in the biotransformation of phenacetin and chlorzoxazone and examined the effect of age on these reactions using liver microsomes from Fischer 344 rats between 3 and 26 months of age. Using rat cDNA-expressed cytochrome P450 (CYP) enzymes, we found that phenacetin biotransformation was primarily mediated by CYP2C6 and CYP1A isoforms, while chlorzoxazone biotransformation was largely mediated by CYP2E1 and CYP1A1. Incubations with liver microsomes prepared from rats of varying ages demonstrated that both phenacetin and chlorzoxazone biotransformation declined with age. Metabolite formation rates in the old rats (25-26 months) were reduced by approximately 60-70% for these reactions. This study suggests that the activity of CYP2E and CYP1A enzymes decline with age in the rat liver. Also, the relative specificity of the index substrates phenacetin (for CYP1A2) and chlorzoxazone (for CYP2E1) in man appears not to be applicable in rats.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-3573
pubmed:author
pubmed:copyrightInfo
Copyright 2004 The Authors
pubmed:issnType
Print
pubmed:volume
56
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
819-25
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Phenacetin and chlorzoxazone biotransformation in aging male Fischer 344 rats.
pubmed:affiliation
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S.