Morphine, a potential inhibitor of myeloperoxidase activity

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.

Repeated Administration of Clinically Relevant Doses of the Prescription Opioids Tramadol and Tapentadol Causes Lung, Cardiac, and Brain Toxicity in Wistar Rats

“…In fact, MPO activity was found to be reduced in lung tissue, relative to the controls, after intravenous administration of 20 mg/kg tramadol in a rat model of ischemia-reperfusion [74]. Interestingly, morphine has been reported as an MPO inhibitor [75], for which a similar effect might be anticipated for other structurally related opioids. Still, tissue quantification of MPO activity would add information on this aspect, since an increase in its levels was reported in rat brain tissue following a 9-week daily treatment with 22.5 to 90 mg/kg tramadol [68].…”

Opioids and Vitamin C: Known Interactions and Potential for Redox-Signaling Crosstalk

“…However, the major antioxidant defense enzymes have been studied in response to opioid exposure: SOD activity has been shown to be decreased in human erythrocytes [ 121 ], plasma [ 12 ], and sperm [ 122 ], as well as in rat cerebrum [ 123 ], hippocampus [ 124 ], and liver [ 125 ]; CAT has been shown to be decreased in human erythrocytes [ 121 ] and plasma [ 12 ], as well as rat cerebrum [ 123 ] and livers [ 125 ]; and GPx has been shown to be decreased in human plasma [ 12 ] and sperm [ 122 ], as well as rat whole brain [ 126 ], cerebrum [ 123 ], and hippocampus [ 124 ], after opioid exposure. Few studies have looked at alternate redox enzymes, but have revealed increases in thioredoxin [ 107 ] as well as decreases in peroxiredoxin [ 127 ] and myeloperoxidase [ 128 ].…”

Effects of Juglone on Neutrophil Degranulation and Myeloperoxidase Activity Related to Equine Laminitis

“…Measurement of the peroxidase activity of MPO was performed with a classical enzymatic assay and the SIEFED assay as described by Nyssen et al (37). The MPO solution was prepared with purified equine or human MPO in the dilution buffer (20 mM PBS, pH 7.4, with 5 g/L BSA and 0.1% Tween-20).…”

“…This assay was performed on the human MPO as its crystallographic (X-ray) structure is wellknown in contrast to that of equine MPO (39). The potential inhibitory effect of juglone was docked in the heme pocket using the GOLD program as described by Nyssen et al (37). Five runs have been performed with the aim to determine the most frequent solutions and ensure their reproducibility.…”