Metabolic disposition of a monoterpene ketone, piperitenone, in rats: Evidence for the formation of a known toxin, p-cresol

K. Madhava Madyastha, Nilesh W. Gaikwad

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22 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)74-80
Number of pages7
JournalDrug Metabolism and Disposition
Volume27
Issue number1
StatePublished - 1999
Externally publishedYes

Fingerprint

Monoterpenes
Metabolites
Ketones
Rats
Mentha
Gas chromatography
Liver Microsomes
Phenobarbital
NADP
Gas Chromatography
Liver
Gas Chromatography-Mass Spectrometry
Mass spectrometry
piperitenone
4-cresol

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Metabolic disposition of a monoterpene ketone, piperitenone, in rats : Evidence for the formation of a known toxin, p-cresol. / Madyastha, K. Madhava; Gaikwad, Nilesh W.

In: Drug Metabolism and Disposition, Vol. 27, No. 1, 1999, p. 74-80.

Research output: Contribution to journalArticle

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