Metabolism and distribution in the rat of peak E substance,a constituent inl-tryptophan product implicated in eosinophilia-myalgia syndrome |
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Authors: | Junko Adachi Takeaki Naito Yasuhiro Ueno Yumi Ogawa Ichiya Ninomiya Yoshitsugu Tatsuno |
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Affiliation: | (1) Department of Legal Medicine, Kobe University School of Medicine, Kusunoki-cho, Chuo-ku, 650 Kobe, Japan;(2) Kobe Women's College of Pharmacy, 658 Kobe, Japan |
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Abstract: | Peak E substance, 1,1-ethylidenebis[tryptophan], a contaminant found inl-tryptophan tablets, has been suggested as a causative agent for eosinophilia-myalgia syndrome (EMS). Peak E substance (50 mg/kg) was administered perorally to Wistar rats to determine its metabolism and distribution. A purification procedure using Bond Elut C8 cartridges followed by HPLC was developed for the determination of peak E substance. The plasma concentration of peak E substance was 136 ng/ml at 1 h, and urinary excretion was 717 ng at 5 h and 10342 ng for 5–24 h, showing slow excretion of peak E substance into urine. The amount of peak E substance in the contents of the large intestine at 5 h, however, was 3136 g, much greater than urinary excretion for 24 h, indicating considerable transfer of peak E substance to large intestine without decomposition by gastric fluid in the stomach. We have detected for the first time not only the occurrence of peak E substance in plasma and urine, but also 1-methyl-tetrahydro--carboline-3-carboxylic acid (MTCA) in blood and organs of rats treated with peak E substance, thereby suggesting MTCA as one of the the metabolites of peak E substance. The amount of MTCA in the contents of the large intestine as well as in urine of rats treated with peak E substance was significantly greater than inl-tryptophantreated rats (50 mg/kg p.o.), demonstrating that MTCA was more readily produced from peak E substance than froml-tryptophan. Finally, we propose acetaldehydeinduced production of MTCA from peak E substance. |
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Keywords: | Peak E substance MTCA font-variant:small-caps" >l-Tryptophan Eosinophilia-myalgia syndrome |
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