The antioxidant N-(2-mercaptopropionyl)-glycine (tiopronin) attenuates expression of neuropathic allodynia and hyperalgesia

Shahid, Muhammad; Subhan, Fazal; Islam, Nazar Ul; Ahmad, Nisar; Farooq, Umar; Abbas, Syed; Akbar, Shehla; Ullah, Ihsan; Raziq, Naila; Din, Zia Ud

doi:10.1007/s00210-020-01995-y

Cited by 9 publications

(6 citation statements)

References 99 publications

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“…Macrophages quickly travel across the perineurium to penetrate the injured nerve trunk, because of the oxidative stress gradient created by Schwann cells, which in turn release more free radicals. Free radicals damage the peripheral nerves and cause hyperexcitability in the afferent nociceptors, which, in combination with central sensitization, causes spontaneous impulses to be generated inside axons and dorsal root ganglions, contributing to the manifestation of neuropathic pain (Shahid et al, 2021). It is also reported that NOX-1 is expressed in neurons (McCann et al, 2008) and microglia of the CNS (Pendyala and Natarajan, 2010), which is confirmed in our study by its elevation in brainstem of CCI rats.…”

Section: Discussionsupporting

confidence: 86%

RETRACTED: Potamogeton perfoliatus L. Extract Attenuates Neuroinflammation and Neuropathic Pain in Sciatic Nerve Chronic Constriction Injury-Induced Peripheral Neuropathy in Rats

et al. 2021

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Sciatic nerve injury is often associated with neuropathic pain and neuroinflammation in the central and peripheral nervous systems. In our previous work, Potamogeton perfoliatus L. displayed anti-inflammatory, antipyretic and analgesic properties, predominantly via the inhibition of COX-2 enzyme and attenuation of oxidative stress. Herein, we extended our investigations to study the effects of the plant’s extract on pain-related behaviors, oxidative stress, apoptosis markers, GFAP, CD68 and neuro-inflammation in sciatic nerve chronic constriction injury (CCI) rat model. The levels of the pro-inflammatory marker proteins in sciatic nerve and brainstem were measured with ELISA 14 days after CCI induction. Pretreatment with the extract significantly attenuated mechanical and cold allodynia and heat hyperalgesia with better potential than the reference drug, pregabalin. In addition, CCI lead to the overexpression of prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), tumor necrosis alpha (TNFα), nuclear factor κB (NF-κB), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and NADPH oxidase-1 (NOX-1) and decreased the catalase level in sciatic nerve and brainstem. The observed neuro-inflammatory changes were accompanied with glial cells activation (increased GFAP and CD68 positive cells), apoptosis (increased Bax) and structural changes in both brainstem and sciatic nerve. The studied extract attenuated the CCI-induced neuro-inflammatory changes, oxidative stress, and apoptosis while it induced the expression of Bcl-2 and catalase in a dose dependent manner. It also decreased the brainstem expression of CD68 and GFAP indicating a possible neuroprotection effect. Taking together, P. perfoliatus may be considered as a novel therapy for neuropathic pain patients after performing the required clinical trials.

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Section: Discussionsupporting

confidence: 86%

RETRACTED: Potamogeton perfoliatus L. Extract Attenuates Neuroinflammation and Neuropathic Pain in Sciatic Nerve Chronic Constriction Injury-Induced Peripheral Neuropathy in Rats

et al. 2021

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“…Western Blot analysis was performed according to the previously described methods, with minor modifications [ 22 , 23 , 24 ]. Briefly, the extracted proteins from the hippocampus of PND-7 were analyzed quantitatively using BioRad protein assay solution.…”

Section: Methodsmentioning

confidence: 99%

“…Although the treatment opportunity to cure ND conditions is not available, there is an increasing range of available therapeutic and supportive options. As therapeutic options, natural products such as phytocompounds have gained esteemed popularity in recent years [ 22 , 23 , 24 ]. Currently, about 75–80% of people of developing countries and about 25% of people of developed countries rely either directly or indirectly on medicinal plants for the first line of treatment [ 25 , 26 , 27 ] as they are considered safer than synthetic drugs [ 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Isolation, Characterization and Neuroprotective Activity of Folecitin: An In Vivo Study

Farooq

Khan

Shah

et al. 2021

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Neurodegenerative diseases (NDs) extend the global health burden. Consumption of alcohol as well as maternal exposure to ethanol can damage several neuronal functions and cause cognition and behavioral abnormalities. Ethanol induces oxidative stress that is linked to the development of NDs. Treatment options for NDs are yet scarce, and natural product-based treatments could facilitate ND management since plants possess plenty of bioactive metabolites, including flavonoids, which typically demonstrate antioxidant and anti-inflammatory properties. Hypericum oblongifolium is an important traditional medicinal plant used for hepatitis, gastric ulcer, external wounds, and other gastrointestinal disorders. However, it also possesses multiple bioactive compounds and antioxidant properties, but the evaluation of isolated pure compounds for neuroprotective efficacy has not been done yet. Therefore, in the current study, we aim to isolate and characterize the bioactive flavonoid folecitin and evaluate its neuroprotective activity against ethanol-induced oxidative-stress-mediated neurodegeneration in the hippocampus of postnatal day 7 (PND-7) rat pups. A single dose of ethanol (5 g/kg body weight) was intraperitoneally administered after the birth of rat pups on PND-7. This caused oxidative stress accompanied by the activation of phosphorylated-c-Jun N-terminal kinase (p-JNK), nod-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), and cysteine-aspartic acid protease-1 (caspase-1) proteins to form a complex called the NLRP3-inflammasome, which converts pro-interleukin 1 beta (IL-1B) to activate IL-1B and induce widespread neuroinflammation and neurodegeneration. In contrast, co-administration of folecitin (30 mg/kg body weight) reduced ethanol-induced oxidative stress, inhibited p-JNK, and deactivated the NLRP3-inflammasome complex. Furthermore, folecitin administration reduced neuroinflammatory and neurodegenerative protein markers, including decreased caspase-3, BCL-2-associated X protein (BAX), B cell CLL/lymphoma 2 (BCL-2), and poly (ADP-ribose) polymerase-1 (PARP-1) expression in the immature rat brain. These findings conclude that folecitin is a flavone compound, and it might be a novel, natural and safe agent to curb oxidative stress and its downstream harmful effects, including inflammasome activation, neuroinflammation, and neurodegeneration. Further evaluation in a dose-dependent manner would be worth it in order to find a suitable dose regimen for NDs.

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“…In turn, ROS promotes central sensitization of dorsal horn cells and activate spinal glial cells (SGCs) through several mechanisms involving the N‐methyl‐D‐aspartate (NMDA) receptor, inhibition of gamma‐aminobutyric acid transmission, and the activation of the transient potential of the receptor superfamily. 14 , 15 , 16 NMDA receptors involved in the pain stimuli transmission are more active during early life, inducing a great release of glutamate. 17 Glutamate, in turn, may trigger both oxidative stress and inflammatory reactions.…”

Section: Pain Oxidative Stress and Brain Development In Preterm Newbornsmentioning

confidence: 99%

“…The increased energy requirement, following pain, causes a greater breakdown of adenosine triphosphate (ATP) into adenosine diphosphate and adenosine monophosphate (AMP), whereas adenosine is converted into hypoxanthine, xanthine, and acid uric, generating ROS. In turn, ROS promotes central sensitization of dorsal horn cells and activate spinal glial cells (SGCs) through several mechanisms involving the N‐methyl‐D‐aspartate (NMDA) receptor, inhibition of gamma‐aminobutyric acid transmission, and the activation of the transient potential of the receptor superfamily 14–16 . NMDA receptors involved in the pain stimuli transmission are more active during early life, inducing a great release of glutamate 17 .…”

Section: Pain Oxidative Stress and Brain Development In Preterm Newbornsmentioning

confidence: 99%

Potential benefits of melatonin to control pain in ventilated preterm newborns: An updated review

et al. 2021

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Infants admitted to neonatal intensive care units are repeatedly stimulated by painful events, especially if intubated. Preterm infants are known to have greater pain perception than full term infants due to immaturity of descending inhibitory circuits and poor noxious inhibitory modulation. Newborns exposed to repetitive painful stimuli are at high risk of impairments in brain development and cognition. Chronic pain is induced and supported by proinflammatory cytokines, free radicals, and reactive oxygen species creating a self‐ sustaining vicious circle. Melatonin is a neurohormone secreted by the pineal gland with antioxidant and anti‐inflammatory functions. This review describes the in‐depth beneficial effects of melatonin for pain control in ventilated preterm newborns. As yet, a minimal amount of literature has been undertaken to consider all its promising bioactivities. The rationale behind the use of melatonin for pain control has also been taken into account in this review. Besides, this review addresses safety concerns and dosages. The potential benefits of melatonin have been assessed against neurological disorders, respiratory distress, microbial infections, and as analgesic adjuvant during ventilation. Additionally, a possible approach for the use of melatonin in ventilated newborns will be discussed.

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The antioxidant N-(2-mercaptopropionyl)-glycine (tiopronin) attenuates expression of neuropathic allodynia and hyperalgesia

Cited by 9 publications

References 99 publications

RETRACTED: Potamogeton perfoliatus L. Extract Attenuates Neuroinflammation and Neuropathic Pain in Sciatic Nerve Chronic Constriction Injury-Induced Peripheral Neuropathy in Rats

RETRACTED: Potamogeton perfoliatus L. Extract Attenuates Neuroinflammation and Neuropathic Pain in Sciatic Nerve Chronic Constriction Injury-Induced Peripheral Neuropathy in Rats

Isolation, Characterization and Neuroprotective Activity of Folecitin: An In Vivo Study

Potential benefits of melatonin to control pain in ventilated preterm newborns: An updated review

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