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 48h 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 6h after treatment. Hepatic GSH levels were almost depleted by single treatment with 1-BB within 6h. 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 24h 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.
Lee
Sang Kyu
SK
College of Pharmacy, Yeungnam University, Gyeongsan 712-749, South Korea.
Lee
Dong Ju
DJ
Ko
Gyu Sub
GS
Yoo
Se Hyun
SH
Ha
Hyun Woo
HW
Kang
Mi Jeong
MJ
Jeong
Tae Cheon
TC
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D008099:Liver / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D009929:Organ Size / Q000187:drug effects; D021241:Spectrometry, Mass, Electrospray Ionization
D006842:Hydrocarbons, Brominated; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; C047757:butyl bromide