Biochemical and Biophysical Research Communications
Biotransformations of R-(+)-pulegone and menthofuran invitro: Chemical basis for toxicity
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FEMA GRAS assessment of natural flavor complexes: Mint, buchu, dill and caraway derived flavoring ingredients
2020, Food and Chemical ToxicologyCitation Excerpt :When S-(−)-pulegone was administered, higher amounts of pulegone, piperitone and benzoic acid and lower amounts of menthofuran were present in the urine, compared to the urine of R-(+)-pulegone treated rats (Madyastha and Gaikwad, 1998). The formation of a γ-ketoenal intermediate from the oxidiation of menthofuran that binds to cellular proteins has been proposed to be related to the observed heptatotoxicity of pulegone (Madyastha and Raj, 1990; McClanahan et al., 1989; Nelson et al., 1992; Thomassen et al., 1992). The higher levels of menthofuran observed in the administration of R-versus S- pulegone was proposed to be correlated with the higher hepatotoxicity of the R-entantiomer observed in mice (Gordon et al., 1982).
Molecular response of Musca domestica L. to Mintostachys verticillata essential oil, (4R)(+)-pulegone and menthone
2012, FitoterapiaCitation Excerpt :In the second major pathway, (4R)-(+)-pulegone is subjected to stereoselective hydroxylation at the C-5 position to form 5-hydroxypulegone, which in turn dehydrates to form p-mentha-1,4(8)-diene-3-one-piperitenone [28]. ( R)(+)-Menthofuran is converted to an α,β-unsaturated-γ-ketoaldehyde, by studies carried out in vivo and in vitro [26,29,30]. Although our results in flies clearly showed the conversion of (4R)(+)-pulegone and menthone into menthofuran, no transformation of this last terpene into further metabolites could be demonstrated, at least in our range of sensitivity (1 μg of terpene/fly).
Criteria for the safety evaluation of flavoring substances: The Expert Panel of the Flavor and Extract Manufacturers Association
2005, Food and Chemical ToxicologyHerbal bioactivation: The good, the bad and the ugly
2004, Life SciencesHepatotoxicity and complementary and alternative medicines
2003, Clinics in Liver DiseaseStereoselective hydroxylation of 4-methyl-2-cyclohexenone in rats: Its relevance to R-(+)-pulegone-mediated hepatotoxicity
2002, Biochemical and Biophysical Research CommunicationsCitation Excerpt :The stereochemical analysis of the unreacted substrate indicated that the reaction is stereoselective and one of the enantiomers is present in excess.The oxygen uptake studies carried out using reconstituted cytochrome P-450 system with R-(+)-pulegone and ±4-methyl-2-cyclohexenone revealed that they were oxygenated at the fastest rates of 11.8 and 1.33 nmol/min/mg protein (νmax) and km were found to be 1.38 and 2.0 μM, respectively. The regio- and stereoselectivity of liver microsomal cytochrome P-450 system play an important role in the metabolism of R-(+)-pulegone [4,6]. Although both the isopropylidene methyl groups in pulegone are allylic to the double bond, it is the methyl group syn to the carbonyl that gets oxidized by the cytochrome P-450 system, which results in the formation of menthofuran, the proximate toxin.