Halothane hepatotoxicity and hepatic free radical metabolism in guinea pigs; the effects of vitamin E

Can J Anaesth. 1996 Jul;43(7):741-8. doi: 10.1007/BF03017960.


Purpose: The aim of this study was to investigate the relation between halothane hepatotoxicity and hepatic free radical metabolism and to establish a possible protective role of vitamin E against halothane hepatotoxicity.

Methods: Twenty-eight guinea pigs were used in the experiments. Halothane (1.5% v/v) in oxygen (100%) was given to the animals for 90 min over three days. Livers from animals were then taken and prepared for the assays. In the enzymatic study, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were measured. As a peroxidation index, the malondialdehyde (MDA) concentration was determined. Also, electron spin resonance (ESR) analysis and electron microscopy (EM) were performed.

Results: Superoxide dismutase (1168.3 +/- 78.2 U.mg-1) and glutathione peroxidase (14.9 +/- 6.2 mIU.mg-1) activities were decreased, but catalase activity (1260.0 +/- 250.6 IU.mg-1) and malondialdehyde concentration (11.5 +/- 1.8 ppb) were increased in liver tissues exposed to halothane compared with control values (1382.2 +/- 91.8 U.mg-1 for SOD, 27.8 +/- 5.2 mIU.mg-1 for GSH-Px, 840.2 +/- 252.4 IU.mg-1 for CAT and 10.0 +/- 1.0 ppb for MDA). Electron spin resonance analysis revealed a peak of CF3CHCl. radical in the exposed tissue. Electron microscopy indicated ultrastructural changes in the hepatic cells of both halothane groups with and without vitamin E treatment.

Conclusion: Halothane causes impairment in the hepatic antioxidant defense system and accelerates peroxidation reactions. As a result, some ultrastructural changes in hepatic tissues occur due to halothane treatment. Although vitamin E prevents peroxidative damage, it does not ameliorate ultrastructural changes caused by halothane treatment. This shows that halothane toxicity results not only from impaired hepatic antioxidant defense system but also from other, unknown causes.

MeSH terms

  • Anesthetics, Inhalation / toxicity*
  • Animals
  • Electron Spin Resonance Spectroscopy
  • Free Radicals
  • Glutathione Peroxidase / metabolism
  • Guinea Pigs
  • Halothane / toxicity*
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / ultrastructure
  • Microscopy, Electron
  • Vitamin E / pharmacology*


  • Anesthetics, Inhalation
  • Free Radicals
  • Vitamin E
  • Glutathione Peroxidase
  • Halothane