Hepatotoxicity and immunotoxicity of 1-bromohexane and its glutathione conjugation in female BALB/c mice

Abstract

Hepatotoxic and immunotoxic effects of 1-bromohexane (1-BH) and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. The animals were treated once orally with 1-BH at 500, 1000, and 2000 mg/kg in corn oil for a dose-response study or treated orally with 1-BH at 2000 mg/kg for 6, 12, 24, and 48 hr for a time-course study. Treatment with 1-BH increased serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) dose dependently. The hepatic contents of thiobarbituric acid reactive substances were significantly increased at 2000 mg/kg of 1-BH from 12 to 24 hr after the treatment. Oral 1-BH at 2000 mg/kg significantly suppressed production of splenic intracellular interleukin (IL)-2 in response to concanavalin A. Following treatment with 1-BH, three GSH conjugates such as S-hexyl GSH, S-hexyl cysteine, and hydroxyhexyl mercapturic acid were identified in livers by liquid chromatography-electrospray ionization tandem mass spectrometry. The hepatic contents of GSH were maximally decreased 6 hr after treatment with 1-BH. GSH conjugates were also detected maximally in livers 6 hr after treatment. These results suggest that 1-BH could cause hepatotoxicity and immunotoxicity as well as depletion of GSH content due to the formation of GSH conjugates with 1-BH in female BALB/c mice. © 2010 The Pharmaceutical Society of Japan.