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Biotransformation of Halothane, Enflurane, Isoflurane, and Desflurane to Trifluoroacetylated Liver Proteins: Association Between Protein Acylation and Hepatic Injury

Njoku, Dolores, Laster, Michael J., Gong, Diane H., Eger, Edmond I, Reed, George F., Martin, Jackie L.·1997·Anesthesia & Analgesia
DOI 10.1097/00000539-199701000-00031
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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 dete…

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Research works printed but not linked: 24

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Metadata

Authors
Njoku, D., Laster, M. J., Gong, D. H., Eger, E. I., Reed, G. F., & Martin, J. L.
Venue
Anesthesia & Analgesia
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
1997-01
Volume
84
Issue
1
Pages
173-178
ISSN
0003-2999
DOI
10.1097/00000539-199701000-00031
Cited by
18
References
1
Language
en

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