Morphine, a potential inhibitor of myeloperoxidase activity

[en] 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. © 2018 Elsevier B.V.

Disciplines :

Physics

Author, co-author :

Nyssen, Pauline ; Université de Liège - ULiège > Département de physique > Spectroscopie biomédicale

Mouithys-Mickalad, Ange ; Université de Liège - ULiège > Centre de l'oxygène : Recherche et développement (C.O.R.D.)

MINGUET, Grégory ; Centre Hospitalier Universitaire de Liège - CHU > Département d'Anesthésie et réanimation > Service d'anesthésie - réanimation

Sauvage, Eric ; Laboratory of Crystallography, Center for Protein Engineering-InBioS, ULiège, Sart-Tilman, Liège, B-4000, Belgium

Wouters, Johan; Laboratoire de Chimie Biologique Structurale, UNamur, Namur, B-5000, Belgium

Franck, Thierry ; Université de Liège - ULiège > Centre de l'oxygène : Recherche et développement (C.O.R.D.)

Hoebeke, Maryse ; Université de Liège - ULiège > Département de physique > Spectroscopie biomédicale

Language :

English

Title :

Morphine, a potential inhibitor of myeloperoxidase activity

Publication date :

October 2018

Journal title :

Biochimica et Biophysica Acta - General Subjects

ISSN :

0304-4165

eISSN :

1872-8006

Publisher :

Elsevier B.V., Netherlands

Volume :

1862

Issue :

Pages :

2236-2244

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 13 November 2020

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