Metabolism of Methylisoeugenol in Liver Microsomes of Human, Rat, and Bovine Origin

  title={Metabolism of Methylisoeugenol in Liver Microsomes of Human, Rat, and Bovine Origin},
  author={Alexander T. Cartus and K H Merz and Dieter Schrenk},
  journal={Drug Metabolism and Disposition},
  pages={1727 - 1733}
Methylisoeugenol (1,2-dimethoxy-4-propenylbenzene, 1) is a minor constituent of essential oils, naturally occurring as a mixture of cis/trans isomers. 1 is a U.S. Food and Drug Administration-approved food additive and has been given “Generally Recognized as Safe” status. Previously, metabolism of 1 has been studied in the rat, revealing mainly nontoxic cinnamoyl derivatives as major metabolites. However, data concerning the possible formation of reactive intermediary metabolites are not… 

Figures and Tables from this paper

Metabolism of the carcinogen alpha-asarone in liver microsomes.

  • A. CartusD. Schrenk
  • Biology, Chemistry
    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
  • 2016

Metabolism of methyleugenol in liver microsomes and primary hepatocytes: pattern of metabolites, cytotoxicity, and DNA-adduct formation.

A virtually complete pattern of microsomal (rat, bovine, and human) and hepatocellular (rat) metabolites of 1 are presented suggesting the formation of several reactive metabolites possibly involved in carcinogenicity, organ toxicity, and immune reactions.

Identification of human and murine sulfotransferases able to activate hydroxylated metabolites of methyleugenol to mutagens in Salmonella typhimurium and detection of associated DNA adducts using UPLC-MS/MS methods.

Several methyleugenol metabolites are activated to DNA-reactive mutagens in S. typhimurium upon incorporation of appropriate sulfation capacity and methods were developed that may be utilised to analyse DNA samples from human tissues specifically for the possible presence of methyle Eugenol adducts.

Structure-Activity Relationships for DNA Damage by Alkenylbenzenes in Turkey Egg Fetal Liver.

Certain alkenylbenzenes (AB), flavoring chemicals naturally occurring in spices and herbs, are established to be cytotoxic and hepatocarcinogenic in rodents, and the DNA damaging potential of key representatives of this class was determined using the Turkey Egg Genotoxicity Assay.

Comparative investigation of the mutagenicity of propenylic and allylic asarone isomers in the Ames fluctuation assay.

α-, β- and γ-asarone are naturally occurring phenylpropenes that occur in different plant families, mainly in Aristolochiaceae, Acoraceae and Lauraceae. Plants containing asarones are used as

Formation of hepatic DNA adducts by methyleugenol in mouse models: drastic decrease by Sult1a1 knockout and strong increase by transgenic human SULT1A1/2.

The role of SULT1A enzymes in the formation of hepatic DNA adducts by methyleugenol in the mouse in vivo was investigated, suggesting an important role of detoxifying pathways for this isomer in vivo.

Genotoxic potential of methyleugenol and selected methyleugenol metabolites in cultured Chinese hamster V79 cells.

Methyleugenol is a substituted alkenylbenzene classified by the European Union's Scientific Committee on Food as a genotoxic carcinogen. We addressed cytotoxicity, genotoxicity and mutagenicity

Insecticidal activities of methyleugenol and β-asarone, from the herbal medicines Saishin and Sekishōkon, and other alkoxy-propenyl-benzene derivatives against the cigarette beetle Lasioderma serricorne (Coleoptera: Anobiidae)

The lack of insecticidal activity of compounds with a hydrogen, hydroxy, or acetoxy substituent in place of one methoxy group indicates that o-dimethoxy groups are essential for Insecticidal activity.

Alkenylbenzenes in Foods: Aspects Impeding the Evaluation of Adverse Health Effects

The current knowledge and the uncertainties impeding a conclusive evaluation of adverse effects to human health possibly resulting from consumption of foods containing alkenylbenzenes are discussed, especially focusing on the genotoxic compounds, safrole, methyleugenol, and estragole.

Bioactivation of herbal constituents: mechanisms and toxicological relevance

The aim of this review is to provide a cataloging of bioactivation mechanisms of herbal substructures, structure-activity relationships, biological targets, and assist in circumventing the structural liability in the development of more effective and safer herb-based NCEs.



Cytochrome P450 mediated bioactivation of methyleugenol to 1'-hydroxymethyleugenol in Fischer 344 rat and human liver microsomes.

The rate of 1'-hydroxylation of methyleugenol in vitro in 13 human liver samples varied markedly (by 37-fold), with the highest activities being similar to the activity evident in control rat liver microsomes, which suggests that the risk posed by dietary ingestion of methylesugenol could vary markedly in the human population.

Metabolism of 2-methylnaphthalene by rat and rainbow trout hepatic microsomes and purified cytochromes P-450.

Differences in the microsome suspension buffers used when preparing microsomes for cytochrome purification as compared to preparing micronaphthalene for direct use appeared to be a significant factor in these differences.

The metabolism of the naturally occurring hepatocarcinogen safrole to 1'-hydroxysafrole and the electrophilic reactivity of 1'-acetoxysafrole.

A conjugated form of 1′-hydroxysafrole was identified as a urinary metabolite of safrole; the conjugate was cleaved by commercial β-glucuronidase preparations. The conjugated 1′-hydroxysafrole

Human cytochrome p450 enzymes of importance for the bioactivation of methyleugenol to the proximate carcinogen 1'-hydroxymethyleugenol.

Kinetic studies revealed that at physiologically relevant concentrations of methyleugenol P450 1A2 is the most important enzyme for bioactivation of methylesugenol in the human liver showing an enzyme efficiency that is approximately 30, 50, and > 50 times higher than the enzyme efficiencies of, respectively, P450 2C9, 2C19, and 2D6.

Metabolism of alkenebenzene derivatives in the rat. II. Eugenol and isoeugenol methyl ethers.

The metabolites of 3,4-dimethoxyallylbenzene and 3,3-methoxypropenylbenzenes were identified and quantitatively determined by g.l.c-mass spectrometry and most of the urinary metabolites were found in the bile.

Safety assessment of allylalkoxybenzene derivatives used as flavouring substances - methyl eugenol and estragole.

  • R. SmithT. Adams I. Sipes
  • Biology
    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
  • 2002

A 28-day feeding study with methyl isoeugenol in rats.

Synthese von Alkylphenolen und ‐pyrocatecholen aus Plectranthus albidus (Labiatae)

Synthesis of Alkylphenols and -catechols from Plectranthus albidus (Labiatae) In the preceding paper, we described the isolation and structure elucidation of a series of even-numbered phenol-

A new cytochrome in liver microsomes.