Morphine Induces Apoptosis, Inflammation, and Mitochondrial Oxidative Stress via Activation of TRPM2 Channel and Nitric Oxide Signaling Pathways in the Hippocampus

Osmanlıoğlu, Haci Ömer; Yıldırım, Mustafa; Akyuva, Yener; Yıldızhan, Kenan; Nazıroğlu, Mustafa

doi:10.1007/s12035-020-01975-6

Cited by 43 publications

(32 citation statements)

References 46 publications

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“…The antioxidant and anti‐inflammatory role of oleuropein is exerted by several mechanisms which enhances the neural defense against several stimuli. Morphine is well‐known for induction of oxidative stress and apoptosis in different regions of brain especially the hippocampus (Osmanlıoğlu et al., 2020). Shibani and co‐workers investigated the protective influence of oleuropein against the morphine induced hippocampal neurotoxicity and memory deficits in male Wistar rats.…”

Section: Neuroprotective Role Of Oleuropeinmentioning

confidence: 99%

Neuroprotective effects of oleuropein: Recent developments and contemporary research

et al. 2021

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Neurological disorders are increasing at a faster pace due to oxidative stress, protein aggregation, excitotoxicity, and neuroinflammation. It is reported that the Mediterranean diet including olives as a major dietary component prevents and ameliorates neurological anomalies. Oleuropein is the major bioactive component in different parts of the Olive (Olea europaea L.) tree. Several mechanisms have been reported for the neuroprotective role of oleuropein including induction of apoptosis and autophagy, enhancing the antioxidant pool of the cerebral region, decreasing the unnecessary release of proinflammatory cytokines and chemokines by deactivating the microglia cells and astrocytes thus preventing the occurrence of neuroinflammation. Regular intake of oleuropein seems to be correlated with decreased risks of neural disorders including Alzheimer's, Parkinson's, strokes, depression, anxiety, epilepsy, and others. This review majorly discusses the chemistry, biosynthesis, and metabolism of oleuropein along with an updated vision of its neuroprotective role in counteracting the acute and chronic neurodegenerative and neuropsychiatric disorders. Moreover, mechanisms by which oleuropein may prevent neurodegeneration are reviewed. Practical application Neurological disorders are negatively affecting the health and life quality of individuals around the globe. Although various medicinal solutions are available to tackle such ailments, none has proven to fully cure and being deprived of side effects. In this respect, the prevention of such disorders using natural remedies may be an effective strategy to overcome the incidence of the increasing cases. Furthermore, the natural compounds provide a safer alternative to pharmaceutical drugs. Hence, oleuropein from olive tree products is found to be efficacious against neurological disorders. This review provides an updated insight on the positive effects of oleuropein against neurodegenerative and neuropsychiatric disorders. The diet practitioners and nutraceutical companies may benefit from the provided information to design and develop strategies to improve the mental health of suffering individuals.

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Section: Neuroprotective Role Of Oleuropeinmentioning

confidence: 99%

Neuroprotective effects of oleuropein: Recent developments and contemporary research

et al. 2021

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“…In addition to 6-OHDA, H 2 O 2 also rapidly increased intracellular Zn 2+ in the SNpc via AMPA receptor activation followed nigral dopaminergic degeneration that is linked with H 2 O 2 -sensitive TRPM2 channel activation. It has been reported that neuron-speci c TRPM2 cation channels may contribute to the pathophysiology of neurological disorders, e.g., cerebral ischemia and oxygen-glucose deprivation [14,[24][25][26][27]. The increase in TRPM2 channel expression enhances the susceptibility to ROS-induced cell death in human neuroblastoma SH-SY5Y cells, a dopaminergic neuronal cell line [28].…”

Section: Discussionmentioning

confidence: 99%

Intracellular Hydrogen Peroxide Produced by 6-Hydroxydopamine is a Trigger for Nigral Dopaminergic Degeneration Via Rapid Influx of Extracellular Zn2+

Nishio

Morioka

Takeuchi

et al. 2021

Preprint

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To elucidate the mechanism of 6-hydroxydopamine (6-OHDA)-induced Zn2+ toxicity, which is involved in neurodegeneration in the substantia nigra pars compacta (SNpc) of rats, we postulated that intracellular hydrogen peroxide (H2O2) produced by 6-OHDA is a trigger for intracellular Zn2+ dysregulation in the SNpc. Intracellular H2O2 level in the SNpc elevated by 6-OHDA was completely inhibited by co-injection of GBR 13069 dihydrochloride (GBR), a dopamine reuptake inhibitor, suggesting that 6-OHDA taken up through dopamine transporters produces H2O2 in the intercellular compartment of dopaminergic neurons. When the SNpc was perfused with H2O2, H2O2 accumulated glutamate in the extracellular compartment and the accumulation was inhibited in the presence of N-(p-amylcinnamoyl)anthranilic acid (ACA), a blocker of the transient receptor potential melastatin 2 (TRPM2) channels. In addition to 6-OHDA, H2O2 also induced intracellular Zn2+ dysregulation via AMPA receptor activation followed by nigral dopaminergic degeneration. Furthermore, 6-OHDA-induced nigral dopaminergic degeneration was completely inhibited by co-injection of HYDROP, an intracellular H2O2 scavenger or GBR into the SNpc. The present study indicates that H2O2 is produced by 6-OHDA taken up through dopamine transporters in the SNpc, is retrogradely transported to presynaptic glutamatergic terminals, activates TRPM2 channels, accumulates glutamate in the extracellular compartment, and induces intracellular Zn2+ dysregulation via AMPA receptor activation, resulting in nigral dopaminergic degeneration. It is likely that intracellular H2O2, but not extracellular H2O2, is a key trigger for nigral dopaminergic degeneration via intracellular Zn2+ dysregulation.

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“…In effect, morphine application may induce inflammatory cytokine expression such as IL-1β, IL-6, and TNF-α, ultimately contributing to inflammation and neurotoxic events. Importantly, it was found that reduced nNOS activation not only enhances the antinociception of morphine but also inhibits the morphine-induced neurotoxicity by downregulating inflammatory mediators (Machelska et al, 1997;Osmanlıoglu et al, 2020). In this regard, MB may also contribute to these events as a potent NOS inhibitor.…”

Section: Inhibited Nos Activation Potentiates Opioidergic Effectsmentioning

confidence: 99%

Methylene Blue Application to Lessen Pain: Its Analgesic Effect and Mechanism

Lee

Han

2021

Front. Neurosci.

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Methylene blue (MB) is a cationic thiazine dye, widely used as a biological stain and chemical indicator. Growing evidence have revealed that MB functions to restore abnormal vasodilation and notably it is implicated even in pain relief. Physicians began to inject MB into degenerated disks to relieve pain in patients with chronic discogenic low back pain (CDLBP), and some of them achieved remarkable outcomes. For osteoarthritis and colitis, MB abates inflammation by suppressing nitric oxide production, and ultimately relieves pain. However, despite this clinical efficacy, MB has not attracted much public attention in terms of pain relief. Accordingly, this review focuses on how MB lessens pain, noting three major actions of this dye: anti-inflammation, sodium current reduction, and denervation. Moreover, we showed controversies over the efficacy of MB on CDLBP and raised also toxicity issues to look into the limitation of MB application. This analysis is the first attempt to illustrate its analgesic effects, which may offer a novel insight into MB as a pain-relief dye.

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Morphine Induces Apoptosis, Inflammation, and Mitochondrial Oxidative Stress via Activation of TRPM2 Channel and Nitric Oxide Signaling Pathways in the Hippocampus

Cited by 43 publications

References 46 publications

Neuroprotective effects of oleuropein: Recent developments and contemporary research

Neuroprotective effects of oleuropein: Recent developments and contemporary research

Intracellular Hydrogen Peroxide Produced by 6-Hydroxydopamine is a Trigger for Nigral Dopaminergic Degeneration Via Rapid Influx of Extracellular Zn2+

Methylene Blue Application to Lessen Pain: Its Analgesic Effect and Mechanism

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