Biotransformation of halothane, enflurane, isoflurane, and desflurane to trifluoroacetylated liver proteins: association between protein acylation and hepatic injury.
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Njoku D, Laster MJ, Gong DH, Eger EI 2nd, Reed GF, Martin JL
Biotransformation of halothane, enflurane, isoflurane, and desflurane to trifluoroacetylated liver proteins: association between protein acylation and hepatic injury.
Anesth Analg. 1997 Jan;84(1):173-8. doi: 10.1097/00000539-199701000-00031.
- PubMed ID
- 8989020 [ View in PubMed]
- Abstract
In susceptible patients, halothane, enflurane, isoflurane, and desflurane can produce severe hepatic injury by an immune response directed against reactive anesthetic metabolites covalently bound to hepatic proteins. The incidence of hepatotoxicity appears to directly correlate with anesthetic metabolism catalyzed by cytochrome P450 2E1 to trifluoroacetylated hepatic proteins. In the present study, we examined whether the extent of acylation of hepatic proteins in rats by halothane, enflurane, isoflurane, and desflurane correlated with reported relative rates of metabolism. After pretreatment with the P450 2E1 inducer isoniazid, five groups of 10 rats breathed 1.25 minimum alveolar anesthetic concentration (MAC) of halothane, enflurane, isoflurane, or desflurane in oxygen, or oxygen alone, each for 8 h. Immunochemical analysis of livers harvested 18 h after anesthetic exposure showed tissue acylation (greatest to least) after exposure to halothane, enflurane, or isoflurane. Reactivity was not different between isoflurane as compared to desflurane or oxygen alone. An enzyme-linked immunosorbent assay showed halothane reactivity was significantly greater than that of enflurane, isoflurane, desflurane, or oxygen, and that enflurane reactivity was significantly greater than desflurane or oxygen. Sera from patients with a clinical diagnosis of halothane hepatitis showed antibody reactivity against hepatic proteins from rats exposed to halothane or enflurane. No reactivity was detected in rats exposed to isoflurane, desflurane, or oxygen alone. These results indicate that production of acylated proteins may be an important mediator of anesthetic-induced hepatotoxicity.
DrugBank Data that Cites this Article
- Drugs
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Enflurane Cytochrome P450 2E1 Protein Humans UnknownSubstrateDetails