Pass, GJ and McLean, SR and Stupans, I and Davies, NW, Microsomal metabolism of the terpene 1,8-cineole in the common brushtail possum (Trichosurus vulpecula), koala (Phascolarctos cinereus), rat and human, Xenobiotica, 31, (4) pp. 205-221. ISSN 0049-8254 (2001) [Refereed Article]
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1. This study reports on the pathways of metabolism and enzyme kinetics of the Eucalyptus terpene, 1,8-cineole, by liver microsomes from the brushtail possum (Trichosurus vulpecula) and koala (Phascolarctos cinereus) (animals that normally include this terpene in their diet), rat and human.
2. The rank order of the ability to metabolize 1,8-cineole with respect to overall 1,8-cineole intrinsic clearance (CL'int = Vmax/Km in Ál mg protein-1 min-1) was koala (188) > possum (181) >>rat (28) > human (12). This order supports the hypothesis that adaptation to a Eucalyptus diet involves enhanced metabolism of terpenes.
3. The metabolism of 1,8-cineole was also studied in the liver from brushtail possum pretreated with a mixture of terpenes, which have previously been shown to induce cytochrome P450 enzymes. Rats were pretreated with the same mixture of terpenes or phenobarbitone.
4. Terpene pretreatment more than doubled the CL'int of 1,8-cineole by brushtail possum liver microsomes (from 180 to 394Ál mgprotein-1 min-1) and increased rat CL'int by nearly 10-fold (from 28 to 259 Ál mgprotein-1 min-1), but still less than the induced possum value. However, phenobarbitone had the greatest inducing effect, increasing the rat CL'int to 1825Ál mg protein-1 min-1.
5. A regioselective preference of oxidation was evident between adapted and nonadapted species. In rat and human oxidation was preferred at the aliphatic ring carbons over methyl substituents. In possum, many of the available carbons were utilized, however metabolism at methyl substituents was preferred. In the koala, oxidation occurred primarily at the methyl substituents.
|Item Type:||Refereed Article|
|Research Division:||Biological Sciences|
|Research Field:||Terrestrial Ecology|
|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)|
|Author:||Davies, NW (Associate Professor Noel Davies)|
|Web of Science® Times Cited:||46|
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