Disease relevance of Eugenol methyl ether

• We investigated the effect of methyleugenol on anaphylaxis [1].
• Two-year toxicity and carcinogenicity study of methyleugenol in F344/N rats and B6C3F(1) mice [2].
• Groups of 10 males and 10 females per sex per species were administered 0, 10, 30, 100, 300 or 1000 mg methyleugenol/kg body weight in 0.5% aqueous methylcellulose by gavage, 5 days per week for 14 weeks [3].
• Additionally, methyleugenol induced hypoproteinemia and hypoalbuminemia, evidenced by decreased total protein and albumin concentrations in both male and female rats, suggesting in inefficiency of dietary protein utilization due to methyleugenol-induced toxic effects on the liver and glandular stomach of rats and mice [3].
• In rats, methyleugenol caused an increase in the incidences of hepatocyte cytologic alteration, cytomegaly, Kupffer cell pigmentation, mixed foci of cellular alteration and bile duct hyperplasia of the liver and atrophy and chronic inflammation of the mucosa of the glandular stomach [3].

High impact information on Eugenol methyl ether

• Twenty of 29 hepatocellular neoplasms from mice treated with methyleugenol had point mutations at codons 32, 33, 34 or 41, sites which are mutated in colon and other cancers [4].
• The activity of S-adenosyl-L-methionine: (iso)eugenol O-methyltransferase (IEMT), a novel enzyme that catalyzes the methylation of the para-4'-hydroxyl of both eugenol and (iso)eugenol to methyleugenol and isomethyleugenol, respectively, was also highest in petal tissue [5].
• The data indicate that even if the tumor response, including molecular alterations, is similar, such as for oxazepam and methyleugenol, early gene expression changes appear to be carcinogen specific and seem to involve apoptosis and cell cycle-related genes [6].
• Cytochrome P450 mediated bioactivation of methyleugenol to 1'-hydroxymethyleugenol in Fischer 344 rat and human liver microsomes [7].
• In control rat liver microsomes, 1'-hydroxylation of methyleugenol (assayed at 20 microM substrate) was inhibited significantly (P < 0.05) by diallylsulfide (40%), p-nitrophenol (55%), tolbutamide (30%) and alpha-naphthoflavone (25%) but not by troleandomycin, furafylline, quinine or cimetidine [7].

Chemical compound and disease context of Eugenol methyl ether

• Methyleugenol (MEG) was tested for toxicity/carcinogenicity in a 2-yr carcinogenesis bioassay because of its widespread use in a variety of foods, beverages, and cosmetics as well as its structural resemblance to the known carcinogen safrole [2].
• Three allylbenzenes from Asiasarum heterotropoides, methyleugenol (1), elemicin (2) and gamma-asaron (3) showed suppressive effects on umu gene expression of the SOS response in the Salmonella typhimurium OY1001/1A2 umu test against the mutagen 2-amino-3,4-dimethylimidazo[4,5-f ]quinoline (MeIQ) [8].

Biological context of Eugenol methyl ether

• In a 2-year bioassay conducted by the National Toxicology Program, methyleugenol caused neoplastic lesions in the livers of Fischer 344 rats and B6C3F(1) mice [9].
• On the other hand, it was shown that elemicin is not synthesized via myristicin but from the possible common precursor, methyleugenol, in the plant having the dominant gene E. These results validate the hypothetical pathways proposed by Hegnauer and Fujita [10].
• 14-Week toxicity and cell proliferation of methyleugenol administered by gavage to F344 rats and B6C3F1 mice [3].
• Based on mortality, body weight gain, clinical chemistry and gross and microscopic evaluation of tissues of rats and mice, the no-observed-effect level (NOEL) of methyleugenol for both species was estimated at 10 mg/kg [3].

Anatomical context of Eugenol methyl ether

• 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 [7].
• These findings imply that generation of protein adducts in livers of rats given methyleugenol in vivo proceeds via the 1'-hydroxy metabolite and requires crucial cofactors, and/or structural features, which are present in intact hepatocytes but not in broken cell preparations and which remain to be defined [11].
• An additional experiment with Gentest microsomes, expressing the same individual enzymes to roughly average liver levels, indicated that P450 1A2, 2C9, 2C19, and 2D6 contribute to methyleugenol 1'-hydroxylation in the human liver [12].
• The effects of methyleugenol (ME) on guinea-pig isolated ileum were studied [13].
• We conclude that methyleugenol directly affect histamine release and HDC gene over-expression in mast cells [1].

Associations of Eugenol methyl ether with other chemical compounds

• Cue-lure response was plesiomorphic to methyl-eugenol response, and the latter has evolved independently within the Bactrocera and Zeugodacus groups of subgenera [14].
• Relaxant and antispasmodic actions of methyleugenol on guinea-pig isolated ileum [13].
• Concurrent incubation of 2000 microM cyclohexane oxide (CHO), an epoxide hydrolase competitor, with a non-cytotoxic concentration of methyleugenol (10 microM) resulted in increased cytotoxicity but had no effect on genotoxicity [9].

Gene context of Eugenol methyl ether

• The mean +/- SD fasting level of methyleugenol in serum was 16.2 +/- 4.0 pg/g wet weight [15].
• Suppression of L-histidine decarboxylase mRNA expression by methyleugenol [1].
• The increase in gastrin and gastric pH of rats and mice given methyleugenol suggests that gastrin feedback was impaired and resulted in conditions not conducive to protein digestion [3].
• Methyleugenol administration to rats induced erythrocyte microcytosis and thrombocytosis in male and female rats [3].

Analytical, diagnostic and therapeutic context of Eugenol methyl ether

• Methyleugenol was found to be a very potent multisite carcinogen in male and female F344/N rats and B6C3F1 mice at all doses tested in 2-year NTP bioassays using gavage dosing [15].
• These polyclonal antisera were shown by enzyme linked immunosorbent assay (ELISA) to contain antibodies which recognized the 3,4-dimethoxyphenyl ring portion of methyleugenol [11].
• The peak levels were within the range of methyleugenol blood levels in the U.S. population, as measured concurrently in a subset of nonfasting participants in the Third National Health and Nutrition Examination Survey (NHANES III) [15].
• Northern-blot analysis demonstrated that significantly reduced level of the mRNA of L-histidine decarboxylase (HDC) was expressed in mast cells treated with methyleugenol, compared to that without methyleugenol [1].
• Determination of methyleugenol in rodent plasma by high-performance liquid chromatography [16].

References