Cell Ultrastructure and Distribution of Trifluoroacetylated Protein-Adducts in Early Hepatic Injury in Mice Induced by Inhalation Anesthetic, Halothane

Halothane is an inhaled, general anesthetic that causes a rare form of severe liver injury by a two-step process. Initial exposure to halothane leads to formation of hepatic trifluoroacetylated protein-adducts (TFAPA) of this drug. These adducts cause hepatocyte injury by an unknown mechanism, resulting in their release into liver tissue and blood circulation, where they come in contact with cells of the immune system. In susceptible patients, TFAPA are recognized as foreign immunogenic proteins. After a second halothane exposure, the resulting liver injury is more severe due to an immune reaction against hepatic TFAPA. Characterization of ultrastructural changes in hepatocytes after initial exposure to halothane may help to elucidate the mechanism of injury as many drug-induced changes in ultrastructure have been observed in the liver [1].