Morphine, a potential inhibitor of myeloperoxidase activity

• Published in: Biochimica et biophysica acta. General subjects Vol. 1862; no. 10; pp. 2236 - 2244
• Main Authors: Nyssen, P., Mouithys-Mickalad, A., Minguet, G., Sauvage, E., Wouters, J., Franck, T., Hoebeke, M.
• Format: Journal Article Web Resource
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2018
• Subjects: analgesic effect; antioxidant activity; ascorbic acid; cytoplasmic granules; cytotoxicity; Docking; electron paramagnetic resonance spectroscopy; enzyme activity; enzyme inhibitors; EPR; gallic acid; hydrogen peroxide; in vitro studies; inflammation; Inhibitor; moieties; molecular models; Morphine; Myeloperoxidase; neutrophils; oxidants; peroxidase; phenanthrenes; Physical, chemical, mathematical & earth Sciences; Physics; Physique; Physique, chimie, mathématiques & sciences de la terre; quercetin; receptors; SIEFED; ultraviolet-visible spectroscopy; SIEFED; Morphine; Myeloperoxidase; Docking; Inhibitor; EPR
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2018.07.007

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. •The inhibitory action of morphine on the myeloperoxidase activity has been investigated.•Morphine acts as a reductive substrate in the peroxidase cycle of MPO.•Morphine protects MPO against the suicide action of its natural substrate, H2O2.•The anti-catalytic action of morphine on MPO is weak.•Morphine could present antioxidant effects during clinical use.