Factors influencing halothane hepatotoxicity in the rat hypoxic model

Richard C. Jee, I. Glenn Sipes, A Jay Gandolfi, Burnell R. Brown

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Halothane, a widely used inhalation anesthetic, was shown to be hepatotoxic to male, phenobarbital-pretreated rats, only when administered under hypoxic conditions (fraction of inspired oxygen = 0.14). The degree of hepatotoxicity as determined from morphological alterations and serum glutamic-pyruvic transaminase (SGPT) activities, correlated well with concentrations of hepatic cytochrome P-450 and concentration of inspired halothane. Maximal lesion intensity developed within 12 to 24 hr after exposure to 1% halothane for as little as 30 min. By 4 days after exposure, the liver had repaired, since no morphological alterations were apparent and SGPT activities had returned to normal values. Female rats, when pretreated with phenobarbital and exposed to 1% halothane under hypoxic conditions did not develop liver injury. SKF-525A and metyrapone reduced the severity of liver injury when administered preanesthesia and 4 hr postanesthesia. The free sulhydryl-containing compounds, cysteine, cystamine, and N-acetylcysteine afforded protection when administered at 4 or 8 hr (cystamine) after ending anesthesia. These results support the hypothesis that reductive or noxoxygen-dependent biotransformation of halothane results in toxic intermediates that can initiate halothane-induced liver injury.

Original languageEnglish (US)
Pages (from-to)267-277
Number of pages11
JournalToxicology and Applied Pharmacology
Volume52
Issue number2
DOIs
StatePublished - 1980

Fingerprint

Halothane
Rats
Liver
Cystamine
Phenobarbital
Alanine Transaminase
Wounds and Injuries
Proadifen
Inhalation Anesthetics
Metyrapone
Poisons
Acetylcysteine
Biotransformation
Serum
Cytochrome P-450 Enzyme System
Cysteine
Reference Values
Anesthesia
Oxygen

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Factors influencing halothane hepatotoxicity in the rat hypoxic model. / Jee, Richard C.; Sipes, I. Glenn; Gandolfi, A Jay; Brown, Burnell R.

In: Toxicology and Applied Pharmacology, Vol. 52, No. 2, 1980, p. 267-277.

Research output: Contribution to journalArticle

Jee, Richard C. ; Sipes, I. Glenn ; Gandolfi, A Jay ; Brown, Burnell R. / Factors influencing halothane hepatotoxicity in the rat hypoxic model. In: Toxicology and Applied Pharmacology. 1980 ; Vol. 52, No. 2. pp. 267-277.
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