Metabolites of dietary 1,8-cineole in the male koala (Phascolarctos cinereus).
The in vivo metabolic fate of 1,8-cineole was investigated in six male koalas. Koalas were fed ad lib a diet of Eucalyptus cephalocarpa leaf with a 1,8-cineole concentration of 2.53+/-0.70% dry mass of leaf, corresponding to a 1,8-cineole intake of 2.4+/-1.1 mmol/kg (3.1+/-1.3 g). Urine and faeces were collected for 24 h and metabolites identified by GC-MS and LC-MS. Metabolites were quantified before and after hydrolysis with beta-glucuronidase to give free and total levels, respectively. Fractional recovery of ingested 1,8-cineole was 1.3+/-0.4 and 1.4+/-0.4 (mean+/-S.D.) for free and total measurements, respectively. Seven metabolites were identified and quantified: 9- and 7-hydroxycineole, 9- and 7-cineolic acid, 7-hydroxy-9-cineolic acid, 9-hydroxy-7-cineolic acid and 7,9-dicineolic acid. The hydroxycineolic acids dominated the metabolite profile (85%). 7,9-Dicineolic acid, a novel metabolite of 1,8-cineole, accounted for almost 10% of the recovered dose making it the second most abundant metabolite after 7-hydroxy-9-cineolic acid (77%). Together, the less oxidised metabolites, the hydroxycineoles and cineolic acid, accounted for only 5% of the cineole consumed. Significant conjugation only occurred with four minor, less oxidised, alcohol and carboxylic acid metabolites. We have shown that the koala detoxifies and eliminates 1,8-cineole primarily by extensive oxidation without utilising conjugation pathways.
Boyle
R
R
Tasmanian School of Pharmacy, University of Tasmania, GPO Box 252-26, 7001, Tasmania, Hobart, Australia. rebecca.boyle@utas.edu.au
McLean
S
S
Foley
W
W
Davies
N W
NW
Peacock
E J
EJ
Moore
B
B
D000818:Animals; D003511:Cyclohexanols; D004032:Diet; D000077591:Eucalyptol; D005243:Feces / Q000737:chemistry; D008658:Inactivation, Metabolic; D008297:Male; D008394:Marsupialia / Q000502:physiology*; D008610:Menthol / Q000031:analogs & derivatives* / Q000378:metabolism*; D039821:Monoterpenes; D010084:Oxidation-Reduction; D013729:Terpenes; D016482:Urinalysis
D003511:Cyclohexanols; D039821:Monoterpenes; D013729:Terpenes; D008610:Menthol; D000077591:Eucalyptol