Mechanisms of Halocarbon-Induced Hepatotoxicity in the Mouse
Final rept. 1 Apr 1989-31 Mar 1990
ARKANSAS UNIV FOR MEDICAL SCIENCES LITTLE ROCK
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Previous studies have shown that high-dose exposure to the halocarbon bromobenzene resulted in hepatotoxicity and lethality that was substantially diminished by co-treatment with the alpha-adrenergic antagonist, phentolamine. The purpose of this study was to compare the hepatoxicity resulting from exposure to the related halocarbons, chlorobenzene, bromobenzene and iodobenzene, and to determine whether the resulting hepatotoxicity could be antagonized by phentolamine. Halobenzene-induced changes in hepatic glutathione concentrations and serum concentrations of catecholamines were determined as possible mediators of hepatic damage. Iodobenzene administration resulted in toxicities similar to that seen with bromobenzene. Administration of either iodobenzene or bromobenzene resulted in hepatotoxicity as measured by serum alanine aminotransferase ALT activity about 1000 fold above normal values. Chlorobenzene was also capable of producing hepatotoxicity, but not to the same extent as iodobenzene. Chlorobenzene-induced hepatotoxicity resulted in serum ALT values approximately 100 fold above normals. Chlorobenzene, bromobenzene or iodobenzene administration significantly decreased hepatic glutathione concentrations to approximately 20 of control concentrations. Phentolamine co- treatments significantly decreased serum ALT activity for all three compounds suggesting that hepatotoxicity might be mediated through an alpha-adrenergic system.