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Canadian Journal of Anaesthesia

, Volume 43, Issue 7, pp 741–748 | Cite as

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

  • I. Durak
  • T. Güven
  • M. Birey
  • H. S. Öztürk
  • Ö. Kurtipek
  • M. Yel
  • B. Dikmen
  • O. Canbolat
  • M. Kavutcu
  • M. Kaçmaz
Laboratory Investigations

Abstract

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 lU · 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 CF3 CHCl 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.

Key words

anaesthetics, volatile: halothane toxicity complications: hepatic toxicity: hepatic 

Résumé

Objectif

Cette étude visait à examiner la relation possible entre l’hépatotoxicité à l’halothane et le métabolisme des radicaux libres et à vérifier si la vitamine E protège contre l’hépatotoxicité à, l’halothane.

Méthodes

Vingt-huit cobayes ont été utilisés. De l’halothane (15% v/v) en oxygène (100%) a été administré aux animaux pendant 90 min sur une période de trois jours. Les foies ont alors été prélevés et préparés pour fin d’analyse. Pour l’étude enzymatique, l’activité de la superoxyde dismutase (SOD), de la glutathione peroxydase (GSH-Px) et de la catalase (CAT) a été mesurée. En tant qu ’indice de la peroxydation, la concentration de la malondialdéhyde (MDA) a été déterminée. En outre, on a procédé à des examens à la résonance paramagnétique électronique (Electronic spin resonance: ESR) et à la microscopie électronique (EM).

Résultats

L’activité de la superoxyde dismutase (1168,3 ±78,2 U · mg−1) et de la glutathione peroxydase (14,9 ± 6,2 UI · mg−1) a diminué, mais celle de la catalase (1260,0 ± 250,6 Ul · mg−1) ainsi que la concentration de ta malondialdéhyde (11,5 ± 1,8 ppb) ont augmenté dans le tissus hépatique exposé à l’halothane comparativement aux valeurs de contrôle (1382,2 ± 91,8U · mg−1 pour SOD, 27,8 ± 5.2 mUI · mg−1 pour SGH-px, 840 ± 252,4 UI · mg−1 pour CAT et 10,0 ± 1,0 ppb pour MDA). La résonance paramagnétique a révélé un pic de radical CF3CHCl dans les tissus exposés. La microscopie électronique a montré des changements ultrastructuraux dans les cellules hépatiques chez les deux groupes halothane traités ou non à la vitamine E.

Conclusion

L’halothane provoque une altération du système de défense hépatique antioxydant et accélère les réactions de peroxydation. Il en résulte des changements ultrastructuraux des tissus hépatiques produits par l’exposition à l’halothane. Bien qu’elle prévienne le dommage peroxydatif, la vitamine E n’atténue pas les changements ultrastucturaux produits par l’exposition à l’halothane. Ceci montre que la toxicité à l’halothane résulte non seulement de l’altération du système de défense antioxydant mais aussi d’autres causes non déterminées.

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Copyright information

© Canadian Anesthesiologists 1996

Authors and Affiliations

  • I. Durak
    • 1
  • T. Güven
    • 2
  • M. Birey
    • 2
  • H. S. Öztürk
    • 1
  • Ö. Kurtipek
    • 3
  • M. Yel
    • 4
  • B. Dikmen
    • 3
  • O. Canbolat
    • 1
  • M. Kavutcu
    • 1
  • M. Kaçmaz
    • 1
  1. 1.Biyokimya A.B.D (Dekanlik Binasy)Ankara UniversitesiSihhiyeTürkíye
  2. 2.Departments of Biology and PhysicsAnkara UniversityAnkaraTurkey
  3. 3.Anaesthesiology Clinics of Ibn-i SinaNumune HospitalsAnkaraTurkey
  4. 4.Department of BiologyGazi UniversityAnkaraTurkey

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