Mechanisms of Halocarbon-Induced Hepatotoxicity in the Mouse
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 30, 1990
- Accession Number
- ADA224022
Entities
People
- Jay Gandy
- Mary A. Smith
Organizations
- University of Arkansas for Medical Sciences