Morphine, a potential inhibitor of myeloperoxidase activity

P. Nyssen, A. Mouithys-Mickalad, G. Minguet, E. Sauvage, J. Wouters, T. Franck, M. Hoebeke

Research output: Contribution to journalArticle

Abstract

Morphine is an opioid alkaloid commonly used in clinical practice for its analgesic properties. The phenolic hydroxyl group of that phenanthrene derivative is pivotal for binding to opioid receptors but it may also be responsible for the antioxidant behavior of morphine reported in several in vitro experiments. In this study, we assessed the effect of morphine on myeloperoxidase (MPO), a hemic enzyme from azurophilic granules of polymorphonuclear neutrophils involved in the production of cytotoxic and microbicidal reactive oxidants during inflammatory response. Specific immunological extraction followed by enzyme detection (SIEFED) and molecular modeling (docking) were performed to study the potential anti-catalytic action of morphine on MPO in comparison with the inhibitory effects of reference antioxidant molecules quercetin, gallic acid and ascorbic acid. The reducing action of morphine on the MPO peroxidase cycle has been investigated using electron paramagnetic resonance (EPR) and UV-visible absorption spectroscopy. Morphine acted as a reducing substrate in the peroxidase cycle of MPO and therefore protected the enzyme against the suicide action of its natural substrate, hydrogen peroxide. The SIEFED experiments associated with the docking study, further demonstrated a lack of strong and sustained anti-catalytic activity of morphine. In summary, from the results of this study, it appears that morphine acts as a weak and reversible inhibitor of MPO that may nonetheless contribute to immunomodulatory and antioxidant effects of this opioid analgesic in vivo.

Original languageEnglish
Pages (from-to)2236-2244
Number of pages9
JournalBiochimica et Biophysica Acta - General Subjects
Volume1862
Issue number10
DOIs
Publication statusPublished - 1 Oct 2018

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Morphine
Peroxidase
Antioxidants
Enzymes
Opioid Analgesics
Gallic Acid
Molecular modeling
Quercetin
Electron Spin Resonance Spectroscopy
Opioid Receptors
Substrates
Absorption spectroscopy
Alkaloids
Oxidants
Hydroxyl Radical
Suicide
Hydrogen Peroxide
Ascorbic Acid
Paramagnetic resonance
Analgesics

Keywords

  • Docking
  • EPR
  • Inhibitor
  • Morphine
  • Myeloperoxidase
  • SIEFED

Cite this

Nyssen, P. ; Mouithys-Mickalad, A. ; Minguet, G. ; Sauvage, E. ; Wouters, J. ; Franck, T. ; Hoebeke, M. / Morphine, a potential inhibitor of myeloperoxidase activity. In: Biochimica et Biophysica Acta - General Subjects. 2018 ; Vol. 1862, No. 10. pp. 2236-2244.
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Morphine, a potential inhibitor of myeloperoxidase activity. / Nyssen, P.; Mouithys-Mickalad, A.; Minguet, G.; Sauvage, E.; Wouters, J.; Franck, T.; Hoebeke, M.

In: Biochimica et Biophysica Acta - General Subjects, Vol. 1862, No. 10, 01.10.2018, p. 2236-2244.

Research output: Contribution to journalArticle

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AU - Mouithys-Mickalad, A.

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