The release of inorganic fluoride from halothane and halothane metabolites by cytochrome P-450, hemin, and hemoglobin.
Halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) releases inorganic fluoride when incubated anaerobically with rat hepatic microsomes reduced with either NADPH or sodium dithionite. Boiled microsomes (cytochrome P-420), hemoglobin, and hemin, each reduced with sodium dithionite, also catalyze the release of inorganic fluoride from halothane, suggesting that the protein portion of cytochrome P-450 is not required for reductive halothane defluorination. 2-Chloro-1,1-difluoroethylene and its bromo analog 2-bromo-1,1-difluoroethylene undergo metabolism in NADPH-reduced microsomes with optimal release of fluoride occurring under air compared to an atmosphere of nitrogen. Neither 2-chloro-1,1,1-trifluoroethane nor 2-bromo-1,1,1-trifluoroethane liberate fluoride in microsomes under air or nitrogen. 2-Chloro-1,1-difluoroethylene and 2-bromo-1,1-difluoroethylene are metabolized predominantly by oxidative cytochrome P-450 metabolism, while reductive pathways utilizing reduced cytochrome P-450, hemoglobin, or hemin liberate fluoride from halothane.
D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005459:Fluorides / Q000378:metabolism*; D006221:Halothane / Q000378:metabolism*; D006418:Heme / Q000031:analogs & derivatives*; D006427:Hemin / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D006454:Hemoglobins; D006418:Heme; D006427:Hemin; D003577:Cytochrome P-450 Enzyme System; D005459:Fluorides; D010100:Oxygen; D006221:Halothane