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The Pharmaceutical Society of Korea (대한약학회)
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Identification of Glutathione Conjugates of 2, 3-Dibromopropene in Male ICR Mice

  • Lee Sang Kyu (College of Pharmacy, Yeungnam University) ;
  • Baik Seo Yeon (College of Pharmacy, Yeungnam University) ;
  • Jeon Tae Won (College of Pharmacy, Yeungnam University) ;
  • Jun In Hye (College of Pharmacy, Yeungnam University) ;
  • Kim Ghee Hwan (College of Pharmacy, Yeungnam University) ;
  • Jin Chun Hua (College of Pharmacy, Yeungnam University) ;
  • Lee Dong Ju (College of Pharmacy, Yeungnam University) ;
  • Kim Jun Kyou (National Institute of Toxicological Research, Korea Food and Drug Administration) ;
  • Yum Young Na (National Institute of Toxicological Research, Korea Food and Drug Administration) ;
  • Jeong Tae Cheon (College of Pharmacy, Yeungnam University)
  • Published : 2006.02.01
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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.

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References

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