The Biology of Morphine and Oxidative Stress

Jia, Jinjing; Xu, Guangtao; Zeng, Xiansi

doi:10.1007/978-3-030-92392-1_102

Cited by 3 publications

(4 citation statements)

References 105 publications

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“…The Fentanyl-dependent group also exhibited a heightened oxidative stress, as evidenced by increased levels of MDA and decreased concentrations of CAT and SOD. Consistent with our findings, previous studies have substantiated that chronic opioid exposure induces oxidative stress through diverse mechanisms, including μ-opioid receptors, phospholipase D2, and NADPH oxidase [ 46 ]. Opioids possess the capacity to activate opioid receptors, initiating the production of free radicals such as reactive oxygen (ROS) or reactive nitrogen (RNS) species, and concurrently diminishing antioxidant activities within target cells [ 47 ].…”

Section: Discussionsupporting

confidence: 92%

Gut Microbiome-Mediated Mechanisms in Alleviating Opioid Addiction with Aqueous Extract of Anacyclus pyrethrum

Baslam,

Kabdy,

Chait

et al. 2024

Biomedicines

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The escalating rates of morbidity and mortality associated with opioid use disorder (OUD) have spurred a critical need for improved treatment outcomes. This study aimed to investigate the impact of prolonged exposure to Fentanyl, a potent opioid, on behavior, biochemical markers, oxidative stress, and the composition of the gut microbiome. Additionally, we sought to explore the therapeutic potential of Anacyclus pyrethrum in mitigating the adverse effects of Fentanyl withdrawal. The study unveiled that chronic Fentanyl administration induced a withdrawal syndrome characterized by elevated cortisol levels (12.09 mg/mL, compared to 6.3 mg/mL for the control group). This was accompanied by heightened anxiety, indicated by a reduction in time spent and entries made into the open arm in the Elevated Plus Maze Test, as well as depressive-like behaviors, manifested through increased immobility time in the Forced Swim Test. Additionally, Fentanyl exposure correlated with decreased gut microbiome density and diversity, coupled with heightened oxidative stress levels, evidenced by elevated malondialdehyde (MDA) and reduced levels of catalase (CAT) and superoxide dismutase (SOD). However, both post- and co-administration of A. pyrethrum exhibited substantial improvements in these adverse effects, effectively alleviating symptoms associated with OUD withdrawal syndrome and eliciting positive influences on gut microbiota. In conclusion, this research underscores the therapeutic potential of A. pyrethrum in managing Fentanyl withdrawal symptoms. The findings indicate promising effects in alleviating behavioral impairments, reducing stress, restoring gut microbiota, and mitigating oxidative stress, offering valuable insights for addressing the challenges of OUD treatment.

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Section: Discussionsupporting

confidence: 92%

Gut Microbiome-Mediated Mechanisms in Alleviating Opioid Addiction with Aqueous Extract of Anacyclus pyrethrum

Baslam,

Kabdy,

Chait

et al. 2024

Biomedicines

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“…Additionally, it has also been shown that PD-related genes (i.e., downregulation of α-synuclein and LRRK2 and upregulation of PARKIN and DJ-1) in rat hippocampus can be improved with exercise coupled with morphine treatment [70]. As the (neuro) biology of the regulatory functions of morphine on oxidative stress is continually being updated [71] more preclinical findings will be compiled.…”

Section: Discussionmentioning

confidence: 99%

Regulation of the Endogenous Opiate Signaling Pathway against Oxidative Stress and Inflammation: A Considerable Approach for Exploring Preclinical Treatment of Parkinson’s Disease

Zhu,

Neuwirth,

Cadet

2023

Pharmacology

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Introduction: Oxidative stress and inflammation are major factors contributing to the progressive death of dopaminergic neurons in Parkinson’s disease (PD). Recent studies have demonstrated that morphine’s biosynthetic pathway, coupled with nitric oxide (NO) release, is evolutionarily conserved throughout animals and humans. Moreover, dopamine is a key precursor for morphine biosynthesis. Method: The present study evaluated a series of preclinical experiments to evaluate the effects of low-level morphine treatment upon neuro-immune tissues exposed to rotenone and 6-OHDA as models of PD, followed by an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation assay and cell/tissue computer-assisted imaging analyses to assess cell/neuronal viability. Results: Morphine at normal physiological concentrations (i.e., 10−6 M and 10−7 M) provided neuroprotection, as it significantly inhibited rotenone and 6-OHDA dopaminergic insults; thereby, reducing and/or forestalling cell death in invertebrate ganglia and human nerve cells. To ensure that morphine caused this neuroprotective effect, naloxone, a potent opiate receptor antagonist, was employed and the results showed that it blocked morphine’s neuroprotective effects. Additionally, co-incubation of NO synthase inhibitor L-NAME also blocked morphine’s neuroprotective effects against rotenone and 6-OHDA insults. Conclusions: Taken together, the present preclinical study showed that while morphine can attenuate lipopolysaccharide-induced inflammation and cell death, both naloxone and L-NAME can abolish this effect. Preincubation of morphine precursors (i.e., L-3,4-dihydroxyphenylalanine, reticuline, and trihexyphenidyl [THP] at physiological concentrations) mimics the observed morphine effect. However, high concentrations of THP, a precursor of the morphine biosynthetic pathway, induced cell death, indicating the physiological importance of morphine biosynthesis in neural tissues. Thus, understanding the morphine biosynthetic pathway coupled with a NO signaling mechanism as a molecular target for neuroprotection against oxidative stress and inflammation in other preclinical models of PD is warranted.

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“…Recent evidence suggests that the deregulated tone in glutamatergic activity is increased by glial immune activation. Opioids, including morphine, have been associated with an increase in both systemic and brain oxidative stress and inflammation 19–22 . Morphine can promote glial activation, and the subsequent increase in oxidative stress and inflammatory markers, by the direct activation of μ‐opioid receptors 23,24 .…”

Section: Introductionmentioning

confidence: 99%

“…Opioids, including morphine, have been associated with an increase in both systemic and brain oxidative stress and inflammation. 19 , 20 , 21 , 22 Morphine can promote glial activation, and the subsequent increase in oxidative stress and inflammatory markers, by the direct activation of μ‐opioid receptors. 23 , 24 In addition, morphine activates a sensor of non‐endogenous molecules, the toll‐like receptor 4 (TLR4), promoting a pro‐inflammatory signaling cascade and upregulation of pro‐inflammatory cytokines.…”

Section: Introductionmentioning

confidence: 99%

Amelioration of morphine withdrawal syndrome by systemic and intranasal administration of mesenchymal stem cell‐derived secretome in preclinical models of morphine dependence

Quezada,

Ponce,

Berríos‐Cárcamo

et al. 2023

CNS Neurosci Ther

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BackgroundMorphine is an opiate commonly used in the treatment of moderate to severe pain. However, prolonged administration can lead to physical dependence and strong withdrawal symptoms upon cessation of morphine use. These symptoms can include anxiety, irritability, increased heart rate, and muscle cramps, which strongly promote morphine use relapse. The morphine‐induced increases in neuroinflammation, brain oxidative stress, and alteration of glutamate levels in the hippocampus and nucleus accumbens have been associated with morphine dependence and a higher severity of withdrawal symptoms. Due to its rich content in potent anti‐inflammatory and antioxidant factors, secretome derived from human mesenchymal stem cells (hMSCs) is proposed as a preclinical therapeutic tool for the treatment of this complex neurological condition associated with neuroinflammation and brain oxidative stress.MethodsTwo animal models of morphine dependence were used to evaluate the therapeutic efficacy of hMSC‐derived secretome in reducing morphine withdrawal signs. In the first model, rats were implanted subcutaneously with mini‐pumps which released morphine at a concentration of 10 mg/kg/day for seven days. Three days after pump implantation, animals were treated with a simultaneous intravenous and intranasal administration of hMSC‐derived secretome or vehicle, and withdrawal signs were precipitated on day seven by i.p. naloxone administration. In this model, brain alterations associated with withdrawal were also analyzed before withdrawal precipitation. In the second animal model, rats voluntarily consuming morphine for three weeks were intravenously and intranasally treated with hMSC‐derived secretome or vehicle, and withdrawal signs were induced by morphine deprivation.ResultsIn both animal models secretome administration induced a significant reduction of withdrawal signs, as shown by a reduction in a combined withdrawal score. Secretome administration also promoted a reduction in morphine‐induced neuroinflammation in the hippocampus and nucleus accumbens, while no changes were observed in extracellular glutamate levels in the nucleus accumbens.ConclusionData presented from two animal models of morphine dependence suggest that administration of secretome derived from hMSCs reduces the development of opioid withdrawal signs, which correlates with a reduction in neuroinflammation in the hippocampus and nucleus accumbens.

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The Biology of Morphine and Oxidative Stress

Cited by 3 publications

References 105 publications

Gut Microbiome-Mediated Mechanisms in Alleviating Opioid Addiction with Aqueous Extract of Anacyclus pyrethrum

Gut Microbiome-Mediated Mechanisms in Alleviating Opioid Addiction with Aqueous Extract of Anacyclus pyrethrum

Regulation of the Endogenous Opiate Signaling Pathway against Oxidative Stress and Inflammation: A Considerable Approach for Exploring Preclinical Treatment of Parkinson’s Disease

Amelioration of morphine withdrawal syndrome by systemic and intranasal administration of mesenchymal stem cell‐derived secretome in preclinical models of morphine dependence

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