Identification of glutathione conjugates of 2, 3-dibromopropene in male ICR mice.
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.
Lee
Sang Kyu
SK
College of Pharmacy, Yeungnam University, Gyeongsan 712-749, South Korea.
Baik
Seo Yeon
SY
Jeon
Tae Won
TW
Jun
In Hye
IH
Kim
Ghee Hwan
GH
Jin
Chun Hua
CH
Lee
Dong Ju
DJ
Kim
Jun Kyou
JK
Yum
Young Na
YN
Jeong
Tae Cheon
TC
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
D000498:Allyl Compounds; C511092:2,3-dibromopropene; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione