title: Halogenated anesthetics form liver adducts and antigens that cross-react with halothane-induced antibodies.
abstract: Two halogenated anesthetics, enflurane and isoflurane, have been associated with an allergic-type hepatic injury both alone and following previous exposure to halothane. Halothane hepatitis appears to involve an aberrant immune response. An antibody response to a protein-bound biotransformation product (trifluoroacetyl adduct) has been detected on halothane hepatitis patients. This study was performed to determine cross-reactivity between enflurane and isoflurane with the hypersensitivity induced by halothane. The subcellular and lobular production of hepatic neoantigens recognized by halothane-induced antibodies following enflurane and isoflurane, and the biochemical nature of these neoantigens was investigated in two animal models. Enflurane administration resulted in neoantigens detected in both the microsomal and cytosolic fraction of liver homogenates and in the centrilobular region of the liver. In the same liver, biochemical analysis detected fluorinated liver adducts that were up to 20-fold greater in guinea pigs than in rats. This supports and extends previous evidence for a mechanism by which enflurane and/or isoflurane could produce a hypersensitivity condition similar to that of halothane hepatitis either alone or subsequent to halothane administration. The guinea pig would appear to be a useful model for further investigations of the immunological response to these antigens.
authors.affiliation: Department of Anesthesiology, College of Medicine, University of Arizona, Tucson 85724, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Clarke
authors.forename: C
authors.initials: C
authors.lastname: Thomas
authors.forename: M
authors.initials: M
authors.lastname: Chen
authors.forename: K L
authors.initials: KL
authors.lastname: Hastings
authors.forename: A J
authors.initials: AJ
authors.lastname: Gandolfi
mesh_terms: D018685:Anesthetics, Inhalation / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000937:Antigen-Antibody Reactions; D003429:Cross Reactions / Q000276:immunology; D004737:Enflurane / Q000276:immunology / Q000378:metabolism; D006168:Guinea Pigs; D006221:Halothane / Q000276:immunology / Q000378:metabolism; D007530:Isoflurane / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018685:Anesthetics, Inhalation; D004737:Enflurane; D007530:Isoflurane; D006221:Halothane