Linked Life Data

11695850

Source:http://linkedlifedata.com/resource/pubmed/id/11695850

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2001-11-6
pubmed:abstractText
1. Oxidation of 1,4-cineole, a monoterpene cyclic ether, was studied in rat and human liver microsomes and recombinant cytochrome P450 (P450 or CYP) enzymes expressed in insect cells in which human P450 and NADPH-P450 reductase cDNAs have been introduced. On analysis with gas chromatography/mass spectrometry, 2-exo-hydroxy-1,4-cineole was identified as a principal oxidation product of 1,4-cineole catalysed by rat and human P450 enzymes. 2. CYP3A4 was a major enzyme involved in the 2-hydroxylation of 1,4-cineole by human liver microsomes, based on the following lines of evidence. First, 1,4-cineole 2-hydroxylation activities catalysed by human liver microsomes were inhibited by ketoconazole, a potent inhibitor of CYP3A activities, and an anti-CYP3A4 antibody. Second, there was a good correlation beteeen CYP3A4 contents and 1,4-cineole 2-hydroxylation activities in liver microsomes of eighteen human samples examined. Finally, of 10 recombinant human P450 enzymes examined, CYP3A4 had the highest activity for 1,4-cineole 2-hydroxylation. 3. Liver microsomal 1,4-cineole 2-hydroxylation activities were induced in rat by pregnenolone 16alpha-carbonitrile and dexamethasone and extensively inhibited by ketoconazole, indicative of the possible roles of CYP3A enzymes in this reaction. 4. Kinetic analysis showed that Vmax/Km for 1,4-cineole 2-hydroxylation catalysed by liver microsomes was higher in a human sample HL-104 (4.6 microM(-1) min(-1)) than those of rat treated with pregnenolone 16alpha-carbonitrile (0.49 microM(-1) min(-1)) and dexamethasone (0.36 microM(-1) min(-1)). 5. 1,8-Cineole, a structurally related monoterpene previously shown to be catalysed by CYP3A enzymes, inhibited 1,4-cineole 2-hydroxylation catalysed by human liver microsomes, whereas 1,4-cineole did not inhibit 1,8-cineole 2-hydroxylation activities. Both compounds caused inhibition of testosterone 6beta-hydroxylation by human liver microsomes, the former compound being more inhibitory than the latter. 6. These results suggest that 1,4-cineole and 1,8-cineole, two plant essential oils present in Citrus medica L. var. acida and Eucalyptus polybractea, respectively, are converted to 2-hydroxylated products by CYP3A enzymes in rat and human liver microsomes. It is unknown at present whether the 2-hydroxylation products of these compounds are more active biologically than the parent compound.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0049-8254
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
713-23
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11695850-Adult, pubmed-meshheading:11695850-Animals, pubmed-meshheading:11695850-Aryl Hydrocarbon Hydroxylases, pubmed-meshheading:11695850-Cells, Cultured, pubmed-meshheading:11695850-Cyclohexanols, pubmed-meshheading:11695850-Cytochrome P-450 CYP3A, pubmed-meshheading:11695850-Cytochrome P-450 Enzyme System, pubmed-meshheading:11695850-Female, pubmed-meshheading:11695850-Flavoring Agents, pubmed-meshheading:11695850-Gas Chromatography-Mass Spectrometry, pubmed-meshheading:11695850-Humans, pubmed-meshheading:11695850-Hydroxylation, pubmed-meshheading:11695850-Insects, pubmed-meshheading:11695850-Kinetics, pubmed-meshheading:11695850-Male, pubmed-meshheading:11695850-Microsomes, Liver, pubmed-meshheading:11695850-Middle Aged, pubmed-meshheading:11695850-Monoterpenes, pubmed-meshheading:11695850-Oxidation-Reduction, pubmed-meshheading:11695850-Oxidoreductases, N-Demethylating, pubmed-meshheading:11695850-Rats, pubmed-meshheading:11695850-Rats, Sprague-Dawley, pubmed-meshheading:11695850-Terpenes, pubmed-meshheading:11695850-Testosterone
pubmed:year
2001
pubmed:articleTitle
Roles of cytochrome P450 3A enzymes in the 2-hydroxylation of 1,4-cineole, a monoterpene cyclic ether, by rat and human liver microsomes.
pubmed:affiliation
Department of Applied Chemistry, Faculty of Science and Engineering, Kinki University, Higashiosaka, Osaka, Japan. miyazawa@apch.kindai.ac.jp
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, Non-U.S. Gov't