Role of glutathione conjugation in the hepatotoxicity and immunotoxicity induced by 1-bromopropane in female BALB/c mice

J Appl Toxicol. 2007 Jul-Aug;27(4):358-67. doi: 10.1002/jat.1214.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Alanine Transaminase / blood
  • Animals
  • Body Weight / drug effects
  • Catalase / metabolism
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / metabolism*
  • Chemical and Drug Induced Liver Injury / pathology
  • Chromatography, Liquid
  • Dose-Response Relationship, Drug
  • Female
  • Glutathione / chemistry
  • Glutathione / metabolism*
  • Glutathione / physiology
  • Hydrocarbons, Brominated / administration & dosage
  • Hydrocarbons, Brominated / toxicity
  • Immunotoxins / administration & dosage
  • Immunotoxins / toxicity*
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Macrophages / drug effects
  • Macrophages / pathology
  • Malondialdehyde / metabolism
  • Mass Spectrometry
  • Mice
  • Mice, Inbred BALB C
  • Microdialysis
  • Organ Size / drug effects
  • Specific Pathogen-Free Organisms
  • Spleen / drug effects
  • Spleen / metabolism
  • Spleen / pathology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / pathology

Substances

  • Hydrocarbons, Brominated
  • Immunotoxins
  • Malondialdehyde
  • Catalase
  • Alanine Transaminase
  • Glutathione
  • 1-bromopropane