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Role of glutathione conjugation in the hepatotoxicity and immunotoxicity induced by 1‐bromopropane in female BALB/c mice
Author(s) -
Lee Sang Kyu,
Jeon Tae Won,
Kim Yong Beom,
Lee Eung Seok,
Jeong Hye Gwang,
Jeong Tae Cheon
Publication year - 2007
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1214
Subject(s) - glutathione , chemistry , pharmacology , antioxidant , corn oil , oral administration , endocrinology , medicine , biochemistry , enzyme , food science
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 with 1‐BP in female BALB/c mice. Copyright © 2007 John Wiley & Sons, Ltd.