Linked Life Data

10548448

Source:http://linkedlifedata.com/resource/pubmed/id/10548448

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1999-12-23
pubmed:abstractText
1. The effects of some biodegradation products of 4-tert-octylphenol ethoxylate (OPEO), namely 4-tert-octylphenol (OP), 4-tert-octylphenol diethoxylate (OP2EO) and 4-tert-octylphenol monocarboxylate (OPIEC) on the kinetics of cytochrome P450 (P450) -dependent monooxygenases in rat liver microsomes have been studied. 2. Testosterone 16beta-hydroxylase (TS16BH), testosterone 2alpha-hydroxylase (TS2AH) and testosterone 6beta-hydroxylase (TS6BH) activities were extensively inhibited by OP at 100 microM (56.0-90.3%). Inhibition was competitive for all P450-dependent monooxygenases. Ki(s) of TS16BH, TS2AH and TS6BH from Lineweaver-Burk plots were 6.37, 3.38 and 34.8 microM respectively. 3. The activities of acetanilide 4-hydroxylase (AA4H), 7-ethoxycoumarin O-deethylase (ECOD) and bufuralol 1'-hydroxylase (BF1'H) were also effectively inhibited by OP at 100 microM (48.6-56.0%). The inhibition of these P450-dependent monooxygenases was non-competitive, and Ki(s) (50.1-63.90 microM) were higher than those of TS16BH, TS2AH and TS6BH. 4. OP2EO also inhibited AA4H, ECOD, TS16BH, TS2AH, BF1'H and TS6BH activities by 38.7-69.3% at 100 microM, although the inhibition rates were slightly lower than those for OP. K(i)s were 14.4-106 microM, and the inhibition was of mixed type (AA4H and ECOD), competitive (TS16BH, TS2AH and TS6BH) and non-competitive (BF1'H). 5. Testosterone 7alpha-hydroxylase (TS7AH), 4-nitrophenol 2-hydroxylase (4NP2H) and lauric acid omega-hydroxylase (LAOH) activities were only slightly affected by OP and OP2EO. 6. The ability of OP1EC to inhibit P450-dependent monooxygenase activities was generally weaker than that of OP and of OP2EO: Ki >200 microM. 7. These results suggest that OPEO biodegradation products interact with constitutive P450 isoforms, CYP1A2, CYP2A2, CYP2B2, CYP2C11 and CYP3A2 in rat liver in vitro (OP > OP2EO > OP1EC), and that the mechanism of this interaction differs depending on the compound and P450 isoform.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0049-8254
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
873-83
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Inhibition of rat hepatic cytochrome P450 activities by biodegradation products of 4-tert-octylphenol ethoxylate.
pubmed:affiliation
Division of Environmental Chemistry, National Institute of Health Sciences, Tokyo, Japan. hanioka@nihs.go.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't