title: Metabolism of (-)-cis- and (-)-trans-rose oxide by cytochrome P450 enzymes in human liver microsomes.
abstract: The in vitro metabolism of (-)-cis- and (-)-trans-rose oxide was investigated using human liver microsomes and recombinant cytochrome P450 (P450 or CYP) enzymes for the first time. Both isomers of rose oxide were incubated with human liver microsomes, and the formation of the respective 9-oxidized metabolite were determined using gas chromatography-mass spectrometry (GC-MS). Of 11 different recombinant human P450 enzymes used, CYP2B6 and CYP2C19 were the primary enzymes catalysing the metabolism of (-)-cis- and (-)-trans-rose oxide. CYP1A2 also efficiently oxidized (-)-cis-rose oxide at the 9-position but not (-)-trans-rose oxide. α-Naphthoflavone (a selective CYP1A2 inhibitor), thioTEPA (a CYP2B6 inhibitor) and anti-CYP2B6 antibody inhibited (-)-cis-rose oxide 9-hydroxylation catalysed by human liver microsomes. On the other hand, the metabolism of (-)-trans-rose oxide was suppressed by thioTEPA and anti-CYP2B6 at a significant level in human liver microsomes. However, omeprazole (a CYP2C19 inhibitor) had no significant effects on the metabolism of both isomers of rose oxide. Using microsomal preparations from nine different human liver samples, (-)-9-hydroxy-cis- and (-)-9-hydroxy-trans-rose oxide formations correlated with (S)-mephenytoin N-demethylase activity (CYP2B6 marker activity). These results suggest that CYP2B6 plays important roles in the metabolism of (-)-cis- and (-)-trans-rose oxide in human liver microsomes.
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Engineering, Kinki University (Kindai University) Kowakae, Higashiosaka-shi, Osaka, 577-8502, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakahashi
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Engineering, Kinki University (Kindai University) Kowakae, Higashiosaka-shi, Osaka, 577-8502, Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Yamamura
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Engineering, Kinki University (Kindai University) Kowakae, Higashiosaka-shi, Osaka, 577-8502, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Usami
authors.affiliation: The Petroleum and Petrochemical College, Chulalongkorn University, Bangkok, 10330, Thailand.
authors.forename: Pramoch
authors.initials: P
authors.lastname: Rangsunvigit
authors.affiliation: The Petroleum and Petrochemical College, Chulalongkorn University, Bangkok, 10330, Thailand.
authors.forename: Pomthong
authors.initials: P
authors.lastname: Malakul
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Engineering, Kinki University (Kindai University) Kowakae, Higashiosaka-shi, Osaka, 577-8502, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Miyazawa
mesh_terms: D000080462:Acyclic Monoterpenes; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002460:Cell Line; D065702:Cytochrome P-450 CYP2B6 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D065731:Cytochrome P-450 CYP2C19 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology; D005503:Food Additives / Q000737:chemistry / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006900:Hydroxylation / Q000187:drug effects; D007700:Kinetics; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D015394:Molecular Structure; D039821:Monoterpenes / Q000737:chemistry / Q000378:metabolism*; D009036:Moths; D009812:Odorants; D010476:Perfume / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D000080462:Acyclic Monoterpenes; D000911:Antibodies, Monoclonal; D065607:Cytochrome P-450 Enzyme Inhibitors; D005503:Food Additives; D039821:Monoterpenes; D010476:Perfume; D011994:Recombinant Proteins; C581370:rose-oxide; C585599:CYP2B6 protein, human; C045793:CYP2C19 protein, human; D065702:Cytochrome P-450 CYP2B6; D065731:Cytochrome P-450 CYP2C19
keywords: CYP2B6; P450; microsomes; monoterpene; rose oxide