IMMUNOLOGICAL STUDIES ON THE MECHANISM OF HALOTHANE-INDUCED HEPATOTOXICITY - IMMUNOHISTOCHEMICAL EVIDENCE OF TRIFLUOROACETYLATED HEPATOCYTES

  • 1 January 1985
    • journal article
    • research article
    • Vol. 233  (3) , 857-862
Abstract
The fulminant hepatotoxicity caused by halothane was thought to have an immunological basis because this toxicity occurs most often after repeated administration of halothane and because sera from patients recovering from severe halothane hepatotoxicity contain antibodies that bind to the surface membranes of hepatocytes of rabbits treated with halothane. The major reactive metabolite of halothane, trifluoroacetyl halide, was studied to determine if it covalently binds to hepatocytes. Specific and sensitive peroxidase enzyme-linked immunosorbent assays and an indirect immunofluorescence staining method for identifying trifluoroacetylated (TFA)-hepatocytes were developed. Liver sections prepared from rats at 4 h after halothane administration were stained preferentially in the centrilobular region with anti-TFA serum whereas livers of control rats showed no staining. The specificity of the assay for the TFA group was confirmed by the complete inhibition of the staining with 200 .mu.M N-.epsilon.-TFA-L-lysine in the diluted antiserum. Halothane (2 mM) or L-lysine did not inhibit this staining. Treatment of rats with deuterated halothane resulted in significantly less staining than did halothane. At 24 h after halothane administration, hepatocytes isolated and stained by indirect immunofluorescence showed a linear and granular pattern on their surface membranes. Trifluoroacetyl halide either reacts directly with constituents of the plasma membranes or with other cellular components which become incorporated into the plasma membranes.

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