Role of glutathione conjugation in 1-bromobutane-induced hepatotoxicity in mice

Halogenated organic compounds, such as 1-bromobutane (1-BB), have been used as cleaning agents, agents for chemical syntheses, or extraction solvents. In the present study, hepatotoxic effects of 1-BB and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. Animals were treated orally with 1-BB at 375, 750 and 1500 mg/kg in corn oil once for dose–response study or treated orally with 1-BB at 1500 mg/kg for 6, 12, 24 and 48 h for time–course study. Three kinds of GSH conjugates, including S-butyl GSH, S-butyl cysteine, and (hydroxybutyl)mercapturic acid, were identified in livers by liquid chromatography–electrospray ionization-tandem mass spectrometry. When the production of S-butyl GSH from 1-BB was investigated in the liver, the conjugate was detected maximally 6 h after treatment. Hepatic GSH levels were almost depleted by single treatment with 1-BB within 6 h. Treatment of mice with 1-BB increased in serum activities of alanine aminotransferase and aspartate aminotransferase dose-dependently. Hepatic contents of thiobarbituric acid reactive substances were significantly increased by 1-BB at 12 and 24 h after treatment. Our present results suggested that 1-BB could cause hepatotoxicity as well as depletion of GSH content, due to the formation of GSH conjugates with 1-BB in mice.