Characterization of hypoxic model for halothane hepatotoxicity

B. R. Brown, I. G. Sipes, R. Jee, A Jay Gandolfi

Research output: Contribution to journalArticle

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Abstract

The two most critical variables necessary to initiate halothane induced liver injury are induction of the hepatic biotransformation enzyme system and a reduced inspired oxygen concentration, which results in an increased rate of halothane biotransformation by the reductive, hepatotoxic pathway. Additional evidence implicating halothane bioactivation as a causative factor is indicated by the inhibition of the lesion by pretreatment of rats with inhibitors of drug metabolism. At present the hypoxic model does not completely correlate with the reported clinical cases of fulminating liver injury following halothane anesthesia. The lesion that develops in rat liver rapidly repairs and does not progress to liver failure. Also, female rats appear resistant. The latter problem has been partially resolved by pretreatment of female rats with testosterone a hormone necessary for maximal microsomal cytochrome P-450 mediated reactions in both male and female rats. Some progress has also been made at prolonging the duration of liver injury by inhibition of liver repair processes with inhibitors of protein synthesis. However, it should be stressed that only a small percentage of animals would be expected to develop progressive liver failure and that only a small number have been studied longer than 2 days post exposure. Perhaps the most exciting finding is the inhibition of lesion development by post-anesthetic treatment with sulfhydryl containing compounds. Cystamine, cysteine and N-acetylcysteine produced nearly complete inhibition when administered 4 hours after end of anesthesia and afford partial protection 8 hours post anesthesia.

Original languageEnglish (US)
JournalAnesthesiology
Volume51
Issue number3 SUPPL
StatePublished - 1979

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Halothane
Liver
Anesthesia
Liver Failure
Biotransformation
Wounds and Injuries
Cystamine
Protein Synthesis Inhibitors
Acetylcysteine
Sulfhydryl Compounds
Cytochrome P-450 Enzyme System
Cysteine
Anesthetics
Testosterone
Hormones
Oxygen
Enzymes
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Characterization of hypoxic model for halothane hepatotoxicity. / Brown, B. R.; Sipes, I. G.; Jee, R.; Gandolfi, A Jay.

In: Anesthesiology, Vol. 51, No. 3 SUPPL, 1979.

Research output: Contribution to journalArticle

Brown, BR, Sipes, IG, Jee, R & Gandolfi, AJ 1979, 'Characterization of hypoxic model for halothane hepatotoxicity', Anesthesiology, vol. 51, no. 3 SUPPL.
Brown, B. R. ; Sipes, I. G. ; Jee, R. ; Gandolfi, A Jay. / Characterization of hypoxic model for halothane hepatotoxicity. In: Anesthesiology. 1979 ; Vol. 51, No. 3 SUPPL.
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