Kupffer cells from halothane-exposed guinea pigs carry trifluoroacetylated protein adducts

Toxicology
S M FurstA J Gandolfi

Abstract

The anesthetic, halothane, is bioactivated by the liver cytochrome P450 system to trifluoroacetyl-chloride, which can readily acylate liver protein. Covalent binding of the trifluoroacetyl moiety may result in hapten formation leading to the induction of an immune response and ultimately halothane hepatitis. In this study the presence of trifluoroacetylated-protein adducts in Kupffer cells was investigated to learn how the immune system might come in contact with the proteins. Guinea pigs were exposed to 1.0% halothane, 40% oxygen for 4 h. Kupffer cells were isolated on days 1 through 9 post-exposure, by liver perfusion and purification by elutriation. Using gel electrophoresis and Western blotting techniques, it has been demonstrated that Kupffer cells obtained from halothane-treated guinea pigs, do carry trifluoroacetyl-protein adducts as recognized by an anti-trifluoroacetyl-rabbit serum albumin antibody. Apparent molecular weights of polypeptides bound by trifluoroacetyl were of a wide range, 25-152 kDa. Bands were most prominent in the larger Kupffer cells with more appearing at lower molecular weights. Trifluoroacetyl-protein adducts were not detected in lung, spleen, lymph node or peripheral blood macrophages. This work ...Continue Reading

References

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Citations

May 14, 1999·European Journal of Drug Metabolism and Pharmacokinetics·P M DansetteD Mansuy
Nov 25, 2003·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Shufeng Zhou
Mar 12, 2013·Pharmacological Reviews·Jack Uetrecht, Dean J Naisbitt
Apr 25, 2014·International Journal of Molecular Sciences·Dolores B Njoku
Mar 8, 2005·Drug Metabolism Reviews·Shufeng ZhouYu-Zong Chen
Oct 4, 2005·Clinica Chimica Acta; International Journal of Clinical Chemistry·Xiao-Xia YangShu-Feng Zhou
May 1, 2007·Current Protocols in Toxicology·Sachin S DeviHarihara M Mehendale
Jul 17, 2003·Current Opinion in Allergy and Clinical Immunology·Béatrice Séguin, Jack Uetrecht
Aug 18, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·S A LongM E Gershwin

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