Abstract
It was shown earlier that the monoterpene ketone, piperitenone (I) is one of the major metabolites of R-(+)-pulegone, a potent hepatotoxin. In the present studies, the metabolic disposition of piperitenone (I) was examined in rats. Piperitenone (I) was administered orally (400 mg/kg of the b. wt./day) to rats for 5 days. The following urinary metabolites were isolated and identified by various spectral analyses: p-cresol (VI), 6,7-dehydromenthofuran (III), p-mentha-1,3,5,8-tetraen-3-ol (IX), p-mentha-1, 3,5-triene-3, 8-diol (X), 5-hydroxypiperitenone (VIII), 7-hydroxypiperitenone (XI), 10-hydroxypiperitenone (XII), and 4-hydroxypiperitenone (VII). Incubation of piperitenone (I) with phenobarbital-induced rat liver microsomes in the presence of NADPH resulted in the formation of five metabolites which have been tentatively identified as metabolites III, VII, VIII, XI, XII, on the basis of gas chromatography retention time and gas chromatography-mass spectrometry analysis. Based on these results, a probable mechanism for the formation of p-cresol from piperitenone (I) via the intermediacy of metabolite III has been proposed.
Footnotes
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Send reprint requests to: Prof. K. M. Madyastha, Bio-organic Section, Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India.
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This investigation was financially supported by JNCASR (Bangalore).
- Abbreviations used are::
- GC
- gas chromatography
- MS
- mass spectrometry
- TLC
- thin-layer chromatography
- IR
- infrared
- Rf
- relative front
- Rt
- retention time
- Received May 29, 1998.
- Accepted August 28, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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