title: Identification of glutathione conjugates of 2, 3-dibromopropene in male ICR mice.
abstract: 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 6 h 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 6 h after the treatment. The present results suggested that 2, 3-DBPE-induced hepatotoxicity might be related with the production of its GSH conjugate.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, South Korea.
authors.forename: Sang Kyu
authors.initials: SK
authors.lastname: Lee
authors.forename: Seo Yeon
authors.initials: SY
authors.lastname: Baik
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Jeon
authors.forename: In Hye
authors.initials: IH
authors.lastname: Jun
authors.forename: Ghee Hwan
authors.initials: GH
authors.lastname: Kim
authors.forename: Chun Hua
authors.initials: CH
authors.lastname: Jin
authors.forename: Dong Ju
authors.initials: DJ
authors.lastname: Lee
authors.forename: Jun Kyou
authors.initials: JK
authors.lastname: Kim
authors.forename: Young Na
authors.initials: YN
authors.lastname: Yum
authors.forename: Tae Cheon
authors.initials: TC
authors.lastname: Jeong
mesh_terms: D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000498:Allyl Compounds / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013997:Time Factors
chemical_list: D000498:Allyl Compounds; C511092:2,3-dibromopropene; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione