Abstract
A possible role of metabolism in 1-bromopropane (1-BP)-induced hepatotoxicity was investigated in male ICR mice. The depletion of glutathione (GSH) by formation of GSH conjugates was associated with increased hepatotoxicity in 1-BP-treated mice. The formation of S-propyl and 2-hydroxypropyl GSH conjugates were identified in the liver following 1-BP treatment. In addition, the formation of reactive metabolites of 1-BP by certain cytochrome P-450 (CYP) may be involved in 1-BP-induced hepatotoxicity. The decreased content of hepatic GSH produced by 1-BP was associated not only with increased activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) but also with elevated levels of hepatic thiobarbituric acid-reactive substance (TBARS) in mice where metabolic enzymes were induced by pretreatment with phenobarbital. In addition, the hepatotoxicity induced by 1-BP was prevented by pretreatment with SKF-525A. Taken together, the formation of reactive metabolites by CYP and depletion of GSH may play important roles in hepatotoxicity induced by 1-BP.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alanine Transaminase / blood
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Animals
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Aspartate Aminotransferases / blood
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Chemical and Drug Induced Liver Injury / etiology
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Chemical and Drug Induced Liver Injury / metabolism*
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Chromatography, High Pressure Liquid
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Cytochrome P-450 Enzyme Inhibitors
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Cytochrome P-450 Enzyme System / metabolism
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Enzyme Induction
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Enzyme Inhibitors / pharmacology
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Glutathione / analogs & derivatives
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Glutathione / drug effects
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Glutathione / metabolism
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Hydrocarbons, Brominated / metabolism
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Hydrocarbons, Brominated / toxicity
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Liver / drug effects
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Liver / metabolism*
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Male
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Mice
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Mice, Inbred ICR
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Phenobarbital / pharmacology
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Proadifen / pharmacology
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Specific Pathogen-Free Organisms
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Spectrometry, Mass, Electrospray Ionization
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Thiobarbituric Acid Reactive Substances / metabolism
Substances
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Cytochrome P-450 Enzyme Inhibitors
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Enzyme Inhibitors
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Hydrocarbons, Brominated
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Thiobarbituric Acid Reactive Substances
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Cytochrome P-450 Enzyme System
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Proadifen
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Aspartate Aminotransferases
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Alanine Transaminase
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Glutathione
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1-bromopropane
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Phenobarbital