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Inhibition of the microsomal metabolism of 1,8-cineole in the common brushtail possum (Trichosurus vulpecula) by terpenes and other chemicals

Citation

Pass, GJ and McLean, SR, Inhibition of the microsomal metabolism of 1,8-cineole in the common brushtail possum (Trichosurus vulpecula) by terpenes and other chemicals, Xenobiotica, 32, (12) pp. 1109-1126. ISSN 0049-8254 (2002) [Refereed Article]


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The definitive published version is available online at: http://www.tandf.co.uk/journals

DOI: doi:10.1080/0049825021000022294

Abstract

1. Brushtail possums (Trichosurus vulpecula) ingest large amounts of terpenes in their diet of Eucalyptus leaf. Previously, we showed that dietary terpenes induce the cytochrome P450 enzymes (CYPs) responsible for their metabolism. The present study examined the effects of various CYP inhibitors on the metabolism of 1,8-cineole, the major dietary terpene, by liver microsomes from the possum and rat.

2. Ketoconazole inhibited the major reactions of terpene-induced microsomes in both species: 9-hydroxylation in the possum and 2-hydroxylation in the rat. This suggests the involvement of CYP3A enzymes, although in the possum there was a lack of the expected inhibition by troleandomycin or activation by α-naphthoflavone, highlighting the differences between species in CYP forms. Diethyldithiocarbamate also inhibited 9-hydroxylation in the possum, indicating that a CYP2E1-like enzyme contributes to this reaction.

3. Three other dietary terpenes were potent competitive inhibitors of 9-hydroxylation in the possum. Ki (M) (mean SE, n=4) were: α-pinene, 4.4 1.1; limonene, 7.8 2.1; p-cymene, 44.3 11.2; cuminyl alcohol (a p-cymene metabolite), 6.0 0.8. It appears likely that p-cymene acts via its metabolite to inhibit 1,8-cineole metabolism.

4. Inhibitory interactions between dietary terpenes, as well as other plant secondary compounds, may impose a significant constraint on foliage consumption in the common brushtail possum, therefore explaining the obligatory generalist nature of this browsing marsupial and other generalist herbivores.

Item Details

Item Type:Refereed Article
Research Division:Biological Sciences
Research Group:Ecology
Research Field:Terrestrial Ecology
Objective Division:Environment
Objective Group:Flora, Fauna and Biodiversity
Objective Field:Forest and Woodlands Flora, Fauna and Biodiversity
Author:Pass, GJ (Ms Georgia Jane Pass)
Author:McLean, SR (Professor Stuart McLean)
ID Code:25547
Year Published:2002
Web of Science® Times Cited:16
Deposited By:Pharmacy
Deposited On:2002-08-01
Last Modified:2015-07-31
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