Archives of Toxicology

, Volume 78, Issue 11, pp 635–642 | Cite as

Relative antioxidant capacities of propofol and its main metabolites

  • Sandrine Boisset
  • Jean-Paul Steghens
  • Patrick Favetta
  • Raphaël Terreux
  • Jérôme Guitton
Molecular Toxicology

Abstract

The antioxidant activity of propofol, a widely used anesthetic, has previously been demonstrated, but no study has focused on propofol metabolites although propofol undergoes extensive metabolism. In the present study, the antioxidant properties of propofol and its metabolites were studied by measuring malondialdehyde (MDA) produced from lipid peroxidation by microsomes triggered with several free radical generating systems. True MDA determination was performed using a specific high performance liquid chromatography technique. Gas chromatography–isotope ratio mass spectrometry methodology was also used to assess the antioxidant action in a homogeneous aqueous environment. Propofol, 2,6-di-isopropyl-1,4-quinol (1,4-quinol) metabolite and 3,5-di-tert-butyl-4-hydroxytoluene markedly inhibit lipid peroxidation at concentrations lower than 5 µM. The binding of the glucuroconjugated moiety to either one of two hydroxyl groups of 1,4-quinol lowers the radical scavenging activity. Propofol glucuronide did not exert any radical scavenging activity except when peroxidation was induced with tert-butylhydroperoxide. Our data demonstrate that propofol and its metabolites inhibit lipid peroxidation at concentrations similar to those measured in human plasma during anesthesia. Their antioxidant efficiency is influenced by several factors, including the type of radical initiator involved and the site of radical production.

Keywords

Propofol Metabolites Free radicals Lipid peroxidation Glucuroconjugate Scavenging activity 

Notes

Acknowledgements

We thank Sarah Somerville for reading of the manuscript carefully. Authors declare that the experiments performed in this paper comply with the current laws of France.

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Sandrine Boisset
    • 1
  • Jean-Paul Steghens
    • 1
  • Patrick Favetta
    • 2
  • Raphaël Terreux
    • 3
  • Jérôme Guitton
    • 4
    • 5
  1. 1.Fédération de BiochimieHôpital E. Herriot, Hospices Civils de LyonLyon Cedex 03France
  2. 2.Faculté des Sciences Institut de Chimie Organique et AnalytiqueOrléans Cedex 2France
  3. 3.Laboratoire de Chimie Physique et Modélisation Moléculaire, Institut des Sciences Pharmaceutiques et Biologiques de LyonUniversité Claude Bernard Lyon ILyon Cedex 08France
  4. 4.Laboratoire de Physiologie Métabolique et Rénale, Inserm U499, Faculté de Médecine Laennec Université Claude Bernard Lyon ILyon Cedex 08France
  5. 5.Laboratoire de Ciblage Thérapeutique en CancérologieCentre Hospitalier Lyon-Sud, Hospices Civils de LyonPierre-BéniteFrance

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