Role of glutathione conjugation in the hepatotoxicity and immunotoxicity induced by 1-bromopropane in female BALB/c mice.
1-Bromopropane (1-BP) is used as a cleaning agent or adhesive solvent in the workplace. In the present study, the hepatotoxic and immunotoxic effects of 1-bromopropane and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. The animals were treated orally with 200, 500 and 1000 mg kg(-1) of 1-BP in corn oil for a dose response study or treated orally with 1000 mg kg(-1) of 1-BP for 6, 12, 24 and 48 h for a time course study. The hepatic and splenic contents of GSH were significantly decreased by 1-BP in a dose-dependent manner. S-propyl GSH was identified in livers following treatment with 1-BP by liquid chromatography-electrospray ionization tandem mass spectrometry. When the production of conjugates from 1-BP was investigated in livers following oral treatment with 1000 mg kg(-1) of 1-BP for 6, 12, 24 and 48 h, the GSH conjugates were detected maximally 6 h after treatment. Treatment of mice with 1-BP increased the serum activity of alanine aminotransferase dose-dependently. The oral 1-BP treatment significantly suppressed the antibody response to a T-dependent antigen and the production of splenic intracellular IL-2 in response to Con A in a dose-dependent manner. The present results suggested that 1-BP could cause hepatotoxicity and immunotoxicity as well as depletion of GSH content due to the formation of GSH conjugates.
Lee
Sang Kyu
SK
College of Pharmacy, Yeungnam University, Gyeongsan, 712-749, South Korea.
Jeon
Tae Won
TW
Kim
Yong Beom
YB
Lee
Eung Seok
ES
Jeong
Hye Gwang
HG
Jeong
Tae Cheon
TC
D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D006842:Hydrocarbons, Brominated / Q000008:administration & dosage / Q000633:toxicity; D000922:Immunotoxins / Q000008:administration & dosage / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D013058:Mass Spectrometry; D051379:Mice; D008807:Mice, Inbred BALB C; D017551:Microdialysis; D009929:Organ Size / Q000187:drug effects; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology
D006842:Hydrocarbons, Brominated; D000922:Immunotoxins; D008315:Malondialdehyde; D002374:Catalase; D000410:Alanine Transaminase; D005978:Glutathione; C118559:1-bromopropane