| Autor: |
Höld KM; Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, 114 Wellman Hall, University of California, Berkeley, CA 94720-3112, USA., Sirisoma NS, Sparks SE, Casida JE |
| Jazyk: |
angličtina |
| Zdroj: |
Xenobiotica; the fate of foreign compounds in biological systems [Xenobiotica] 2002 Apr; Vol. 32 (4), pp. 251-65. |
| DOI: |
10.1080/00498250110095745 |
| Abstrakt: |
1. Hyssop oil is an important food additive and herbal medicine and the principal active ingredients are (-)-cis- and (-)-trans-3-pinanones. No information is available on their metabolism or specific mode of action. 2. The metabolites of cis- and trans-3-pinanones were examined from mouse and human liver microsomes and human recombinant P4503A4 with NADPH and on administration to mouse by gas chromatography/chemical ionization mass spectrometry comparison with standards from synthesis. 3. The major metabolite of cis-3-pinanone in each P450 system and in brain of the i.p.-treated mouse in quantitative studies was 2-hydroxy-cis-3-pinanone, and two minor metabolites were hydroxypinanones other than 2-hydroxy-trans-3-pinanone and 4S-hydroxy-cis-3-pinanone. The urine from oral cis-3-pinanone treatment examined on a qualitative basis contained conjugates of metabolites observed in the microsomal systems plus 2,10-dehydro-3-pinanone. 4. Trans-3-pinanone was metabolized more slowly than the cis-isomer in each system to give hydroxy derivatives different than those derived from cis-3-pinanone. 5. Cis- and trans-3-pinanones and hyssop oil act as gamma-aminobutyric acid type A (GABAA) receptor antagonists based on inhibition of 4'-ethynyl-4-n-[2,3-(3)H(2)]propylbicycloorthobenzoate ([(3)H]EBOB) binding in mouse brain membranes (IC(50) of 35-64 microM) and supported by tonic/clonic convulsions in mouse (i.p. LD(50) 175 to >250 mg kg(-1)) alleviated by diazepam. The cis-3-pinanone metabolites 2-hydroxy-cis-3-pinanone and 2,10-dehydro-3-pinanone exhibit reduced toxicity and potency for inhibition of [(3)H]EBOB binding. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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