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J.Health Sci., 56(4), 434-441, 2010
-Regular Article-
Hepatotoxicity and Immunotoxicity of 1-Bromohexane and Its Glutathione Conjugation in Female BALB/c Mice
Sang Kyu Lee,a Dong Ju Lee,a
Hyun Woo Ha,a Jin Woo Yoo,a
Gyu Sub Ko,a Mi Jeong Kang,a
Wonku Kang,b Hye Gwang Jeong,c
Kyung Bok Lee,d and Tae Cheon Jeong*, a
aCollege of Pharmacy, Yeungnam University, 214-1, Dae-dong, Gyeongsan 712-749, Korea,
bCollege of Pharmacy, Catholic University of Daegu, 330, Geumlak-ri, Gyeongsan 712-702, Korea,
cCollege of Pharmacy, Chungnam National University, 220 Gung-dong, Daejeon 305-764, Korea and
dCollege of Medicine, Konyang University, 119, Daehak-ro, Nonsan 320-711, Korea
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.
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