KMID : 0043320060290020172
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Archives of Pharmacal Research 2006 Volume.29 No. 2 p.172 ~ p.177
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Identification of Glutathione Conjugates of 2, 3-Dibromopropene in Male ICR Mice
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Lee Sang-Kyu
Baik Seo-Yeon Jeon Tae-Won Jun In-Hye Kim Ghee-Hwan Jin Chun-Hua Lee Dong-Ju Kim Jun-Kyou Yum Young-Na Jeong Tae-Cheon
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Abstract
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Hepatotoxic potential of 2, 3-dibromopropene (2, 3-DBPE) and its conjugation with glutathione (GSH) were investigated in male ICR mice. Treatment of mice with 20, 50, and 100 mg/kg of 2, 3-DBPE for 24 h caused elevation of serum alanine aminotransferase and aspartate aminotransferase activities. The hepatic content of GSH was not changed by 2, 3-DBPE. Meanwhile, the GSH content was slightly reduced when mice were treated with 2, 3-DBPE for 6h and significantly increased 12 h after the treatment. Subsequently, a possible formation of GSH conjugate of 2, 3-DBPE was investigated in vivo. After the animals were treated orally with 20, 50, and 100 mg/kg of 2, 3-DBPE, the animals were subjected to necropsy 6, 12, and 24 h later. A conjugate of S-2-bromopropenyl GSH was identified in liver and serum treated with 100 mg/kg of 2, 3-DBPE by using liquid chromatography-electrospray ionization tandem mass spectrometry. The protonated molecular ions [M+H]+ of S-2-bromopropenyl GSH were observed at m/z 425.9 and 428.1 in the positive ESI spectrum with a retention time of 6.35 and 6.39 min, respectively. In a time-course study in livers following an oral treatment of mice with 100 mg/kg of 2, 3-DBPE for 6, 12, and 24 h, the 2, 3-DBPE GSH conjugate was detected maximally 6h after the treatment. The present results suggested that 2, 3-DBPE-induced hepatotoxicity might be related with the production of its GSH conjugate.
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KEYWORD
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2, 3-Dibromopropene, Hepatotoxicity, Glutathione conjugate, LC/ESI-MS
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