Hepatic Metabolism of Methyl Anthranilate and Methyl N-Methylanthranilate as Food Flavoring Agents in Relation to Allergenicity in the Guinea Pig

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概要

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• To assess the safety of the food flavoring agents, methyl anthranilate (MA) and methyl N-methylanthranilate (MNMA), their relationships with metabolism and allergenicity were examined in guinea pigs. Both MA and MNMA were hydrolyzed to anthranilic acid (AA) and N-methylanthranilic acid (N-methylAA), respectively, by guinea pig liver microsomes. These hydrolytic activities at 1000μM were 320 and 35nmol/min/mg protein, respectively. Moreover, MNMA was N-demethylated to MA by the liver microsomes; the oxidative activity at 1000μM of MNMA was 2.8nmol/min/mg protein. The N-demethylase activity for N-methylAA at 1000μM in the liver microsomes was 3.9nmol/min/mg protein. Kinetic analysis indicated that the V_<max>/K_m values of MA and MNMA hydrolyses were 15- and 7.4-fold greater in guinea pig liver microsomes than in the cytosol, respectively, suggesting that these hydrolytic activities were predominantly localized in the microsomes. Liver microsomal activities for the hydrolysis of these flavoring esters were markedly inhibited by diisopropyl fluorophosphate, phenylmethylsulfonyl fluoride, and bis(pnitrophenyl)phosphate but not by physostigmine. These hydrolytic activities were suppressed by aspirin, a substrate of carboxylesterase, in a concentration-dependent manner. The N-demethylations of MNMA and N-methylAA were inhibited by SKF 525-A, a nonselective inhibitor of cytochrome P450. At the same time as the metabolic study described above, skin reactions in guinea pigs were investigated using MA, MNMA, N-methylAA, and AA. All compounds examined elicited positive skin reactions, although MNMA and AA exhibited relatively greater sensitizing properties. These results may provide useful information about metabolism in the toxicologic evaluations of MA and MNMA.

• 社団法人日本薬学会の論文
• 2005-12-01

著者

• YAMAMOTO IKUO

  Department of Laboratory Medicine, Miyazaki Medical College

• 景山 節

  京大・霊長類研・生化学

• Yamamoto Ikuo

  Department Of Hygienic Chemistry School Of Pharmaceutical Sciences Kyushu University Of Health And W

• Yamaori Satoshi

  Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University

• Funahashi Tatsuya

  Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University

• Kimura Toshiyuki

  Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University

• Watanabe Kazuhito

  Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University

• Yokozuka Hisayo

  Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University

• Sasama Aya

  Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University

• YAMAMOTO Ikuo

  School of Pharmaceutical Sciences, Kyushu University of Health and Welfare

• Yamamoto Ikuo

  北陸大学 薬 衛化

• Yamamoto Ikuo

  Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University

• YAMAMOTO IKUO

  Hygienic Chemistry

• Kimura T

  Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University

• 景山 節

  京都大学霊長類研究所人類進化モデル研究センター

• 景山 節

  京大・霊長研

• Yamaori Satoshi

  Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University

• Kimura Toshiyuki

  Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University

• Watanabe Kazuhito

  Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University

• Watanabe Kazuhito

  Department Of Chemistry And Chemical Engineering Faculty Of Engineering Yamagata University

• Funahashi Tatsuya

  Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University

• Kimura T

  Department Of Medicinal Chemistry Center For Frontier Research In Medicinal Science 21st Century Coe

• Sasama Aya

  Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University

• Yamamoto I

  Hokuriku Univ. Kanazawa Jpn

• Yamamoto I

  Hygienic Chemistry

• Yokozuka Hisayo

  Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University

• Watanabe Kazuhito

  Faculty Of Pharmaceutical Sciences Kyushu University

• Yamamoto Ikuo

  Hygienic Chemistry School Of Pharmacy Hokuriku University

• Yamamoto Ikuo

  Department Of Bioapplied Chemistry Faculty Of Engineering Osaka City University

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