Hepatotoxic and immunotoxic effects produced by 1,3-dibromopropane and its conjugation with glutathione in female BALB/c mice.

To determine a possible role of glutathione (GSH) conjugation in 1,3-dibromopropane (1,3-DBP)-induced hepatotoxicity and immunotoxicity, female BALB/c mice were treated orally with 1,3-DBP. Based on the liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS) analyses, two forms of S-bromopropyl GSH were observed at m/z 427.9 and 429.9 in the positive ESI spectrum with a retention time of 5.29 and 5.23 min, respectively. Following single treatment of mice with 150, 300 or 600 mg/kg 1,3-DBP for 12 hr, the amount of S-bromopropyl GSH was detected maximally in liver homogenates at 600 mg/kg 1,3-DBP. Hepatic GSH levels were significantly decreased by treatment with 1,3-DBP. In a time course study, production of S-bromopropyl GSH rose maximally 6 hr after treatment and decreased gradually thereafter. The liver weights were significantly increased by treatment with 600 mg/kg 1,3-DBP. When mice were treated orally with 600 mg/kg 1,3-DBP for 12 hr, the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were increased by 365- and 83-fold. In addition, oral 1,3-DBP significantly suppressed the antibody response to a T-dependent antigen at 600 mg/kg 1,3-DBP. 1,3-DBP elevated hepatic levels of malondialdehyde and suppressed the activities of some hepatic enzymes involved in anti-oxidation. Taken together, the formation of GSH conjugate with 1,3-DBP may deplete cellular GSH and, subsequently, produce hepatotoxicity and immunotoxicity via damage to the cellular anti-oxidative system.