Role of glutathione conjugation in 1-bromobutane-induced hepatotoxicity in mice

Title
Role of glutathione conjugation in 1-bromobutane-induced hepatotoxicity in mice
Author(s)
이상규이동주고규섭유진우하현우강미정정태천
Keywords
FEMALE BALB/C MICE; TANDEM MASS-SPECTROMETRY; ISOLATED RAT HEPATOCYTES; LIPID-PEROXIDATION; DEPLETION; IDENTIFICATION; 1-BROMOPROPANE; TOXICITY; ACID
Issue Date
201010
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Citation
FOOD AND CHEMICAL TOXICOLOGY, v.48, no.10, pp.2707 - 2711
Abstract
Halogenated organic compounds, such as 1-bromobutane (1-BB), have been used as cleaning agents, agents for chemical syntheses, or extraction solvents. In the present study, hepatotoxic effects of 1-BB and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. Animals were treated orally with 1-BB at 375, 750 and 1500 mg/kg in corn oil once for dose-response study or treated orally with 1-BB at 1500 mg/kg for 6, 12, 24 and 48 h for time-course study. Three kinds of GSH conjugates, including S-butyl GSH, S-butyl cysteine, and (hydroxybutyl)mercapturic acid, were identified in livers by liquid chromatography-electrospray ionization-tandem mass spectrometry. When the production of S-butyl GSH from 1-BB was investigated in the liver, the conjugate was detected maximally 6 h after treatment. Hepatic GSH levels were almost depleted by single treatment with 1-BB within 6 h. Treatment of mice with 1-BB increased in serum activities of alanine aminotransferase and aspartate aminotransferase dose-dependently. Hepatic contents of thiobarbituric acid reactive substances were significantly increased by 1-BB at 12 and 24 h after treatment. Our present results suggested that 1-BB could cause hepatotoxicity as well as depletion of GSH content, due to the formation of GSH conjugates with 1-BB in mice. (C) 2010 Elsevier Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/23528http://dx.doi.org/10.1016/j.fct.2010.06.044
ISSN
0278-6915
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약학대학 > 약학부 > Articles
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