scholarly journals Flavonoids Alleviate Peripheral Neuropathy Induced by Anticancer Drugs

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1576
Author(s):  
Manaal Siddiqui ◽  
Basma Abdellatif ◽  
Kevin Zhai ◽  
Alena Liskova ◽  
Peter Kubatka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Proinflammatory Cytokine ◽  
Microglial Activation ◽  
Neuronal Damage ◽  
Thermal Hyperalgesia ◽  
Future Research ◽  
Cytokine Release ◽  
Channel Activation ◽  
Cold Allodynia ◽  
Clinical Benefits

Purpose: This study aimed to assess the potential of flavonoids in combating CIPN. Methods: PubMed and Google Scholar were used, and studies that investigated flavonoids in models of CIPN and models of neuropathic pain similar to CIPN were included. Only studies investigating peripheral mechanisms of CIPN were used. Results: Flavonoids inhibit several essential mechanisms of CIPN, such as proinflammatory cytokine release, astrocyte and microglial activation, oxidative stress, neuronal damage and apoptosis, mitochondrial damage, ectopic discharge, and ion channel activation. They decreased the severity of certain CIPN symptoms, such as thermal hyperalgesia and mechanical, tactile, and cold allodynia. Conclusions: Flavonoids hold immense promise in treating CIPN; thus, future research should investigate their effects in humans. Specifically, precise pharmacological mechanisms and side effects need to be elucidated in human models before clinical benefits can be achieved.

scholarly journals The Contribution of Microglia to Neuroinflammation in Parkinson’s Disease

2021 ◽  
Vol 22 (9) ◽  
pp. 4676
Author(s):  
Katja Badanjak ◽  
Sonja Fixemer ◽  
Semra Smajić ◽  
Alexander Skupin ◽  
Anne Grünewald
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Inflammatory Cytokine ◽  
Population Ageing ◽  
Future Research ◽  
Cytokine Release ◽  
Vicious Cycle ◽  
Inflammatory Processes ◽  
Great Evidence

With the world’s population ageing, the incidence of Parkinson’s disease (PD) is on the rise. In recent years, inflammatory processes have emerged as prominent contributors to the pathology of PD. There is great evidence that microglia have a significant neuroprotective role, and that impaired and over activated microglial phenotypes are present in brains of PD patients. Thereby, PD progression is potentially driven by a vicious cycle between dying neurons and microglia through the instigation of oxidative stress, mitophagy and autophagy dysfunctions, a-synuclein accumulation, and pro-inflammatory cytokine release. Hence, investigating the involvement of microglia is of great importance for future research and treatment of PD. The purpose of this review is to highlight recent findings concerning the microglia-neuronal interplay in PD with a focus on human postmortem immunohistochemistry and single-cell studies, their relation to animal and iPSC-derived models, newly emerging technologies, and the resulting potential of new anti-inflammatory therapies for PD.

scholarly journals Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by α-Synuclein Fibrillary Aggregates

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 776 ◽  
Author(s):  
Acuña ◽  
Hamadat ◽  
Corbalán ◽  
González-Lizárraga ◽  
dos-Santos-Pereira ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Microglial Activation ◽  
Microglial Cell ◽  
Inflammatory Responses ◽  
Parent Compound ◽  
Cytokine Release ◽  
Autoxidation Product ◽  
Pi3k Inhibition ◽  
Inflammatory Processes

: Aggregated forms of the synaptic protein α-synuclein (αS) have been proposed to operate as a molecular trigger for microglial inflammatory processes and neurodegeneration in Parkinson´s disease. Here, we used brain microglial cell cultures activated by fibrillary forms of recombinant human αS to assess the anti-inflammatory and neuroprotective activities of the antibiotic rifampicin (Rif) and its autoxidation product rifampicin quinone (RifQ). Pretreatments with Rif and RifQ reduced the secretion of prototypical inflammatory cytokines (TNF-, IL-6) and the burst of oxidative stress in microglial cells activated with αS fibrillary aggregates. Note, however, that RifQ was constantly more efficacious than its parent compound in reducing microglial activation. We also established that the suppressive effects of Rif and RifQ on cytokine release was probably due to inhibition of both PI3K- and non-PI3K-dependent signaling events. The control of oxidative stress appeared, however, essentially dependent on PI3K inhibition. Of interest, we also showed that RifQ was more efficient than Rif in protecting neuronal cells from toxic factors secreted by microglia activated by αS fibrils. Overall, data with RifQ are promising enough to justify further studies to confirm the potential of this compound as an anti-parkinsionian drug.

scholarly journals Pre-emptive PPAR-γ Activation Abolishes Development of Nerve Injury-induced Behavioral Hypersensitivity: Elucidating Underlying Mechanisms

2021 ◽  
pp. 23-37
Author(s):  
Seema Thakur ◽  
Haritha Pasupulati ◽  
Saurabh Sharma ◽  
Satyanarayana S. V. Padi
Keyword(s):  
Oxidative Stress ◽  
Neuropathic Pain ◽  
Nerve Injury ◽  
Chronic Constriction Injury ◽  
Thermal Hyperalgesia ◽  
Plasma Extravasation ◽  
Painful Condition ◽  
Cold Allodynia ◽  
Ppar Γ ◽  
Underlying Mechanisms

Background: Neuropathic pain is a chronic incapacitating painful condition for which there is no effective treatment. The peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear transcription factors that play key roles in modulating immune and inflammatory responses. The antinociceptive properties of PPAR-γ activation on development of neuropathic pain are not fully known. Objective: To determine the role of PPAR-γ activation on the development of neuropathic pain following chronic constriction injury and to elucidate underlying mechanisms. Methodology: Neuropathy was induced by chronic constriction injury of sciatic nerve in rats. Cold allodynia and thermal hyperalgesia were assessed and the markers of inflammation and nitroso-oxidative stress were estimated. Results: Pre-emptive administration of pioglitazone, a PPAR-γ agonist (3, 10 or 30 mg/kg, i.p. 1 hr before surgery and continued once daily for 2 weeks) dose-dependently attenuated paw withdrawal latency to cold (allodynia) and thermal (hyperalgesia) stimuli. Pioglitazone significantly reduced elevated TBARS, protein carbonylation, nitrite levels and markedly restored depleted GSH, and reduction in activities of SOD and catalase in injured nerves. Further, pioglitazone markedly reduced plasma extravasation and levels of pro-inflammatory cytokines TNF-α and IL-1β following nerve injury. Moreover, pioglitazone did not alter the locomotor activity. Pretreatment with PPAR-γ antagonist BADGE (30 mg/kg, i.p.) blocked the beneficial effects of pioglitazone. Essentially, pioglitazone promoted the long-lasing recovery and also prevented the development of neuropathic pain even after treatment termination. Conclusion: Pioglitazone, a PPAR-γ agonist receptor-dependently abolished the development of traumatic neuropathic pain and exerted long-lasting antinociceptive effects through reducing nitroso-oxidative stress and inflammation. Our findings strongly suggest that pre-emptive activation of PPAR-γ prevented or at least delayed the development of nerve injury-induced pain hypersensitivity.

scholarly journals Methane-Rich Saline Alleviates CA/CPR Brain Injury by Inhibiting Oxidative Stress, Microglial Activation-Induced Inflammatory Responses, and ER Stress-Mediated Apoptosis

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Ruixia Cui ◽  
Sinan Liu ◽  
Cong Wang ◽  
Tong Liu ◽  
Jie Ren ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Arrest ◽  
Brain Injury ◽  
Er Stress ◽  
Microglial Activation ◽  
Inflammatory Responses ◽  
Neuronal Damage ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1

Brain injury induced by cardiac arrest/cardiopulmonary resuscitation (CA/CPR) is the leading cause of death among patients who have recovery of spontaneous circulation (ROSC). Inflammatory response, apoptosis, and oxidative stress are proven pathological mechanisms implicated in neuronal damage. Methane-rich saline (MRS) has been proven that exerts a beneficial protectiveness impact in several models of ischemia-reperfusion injury. The goal of this paper is to ascertain the role of MRS in CA/CPR-induced brain injury and its potential mechanisms. The tracheal intubation of Sprague-Dawley (SD) rats was clamped for 6 min to establish an asphyxiating cardiac arrest model. After that, chest compressions were applied; then, MRS or saline was administered immediately post-ROSC, the rats were sacrificed, and brain tissue was collected at the end of 6 hours. We observed that MRS treatment attenuated neuronal damage in the hippocampal CA1 region by inhibiting microglial activation, leading to a decrease in the overexpression of proinflammatory cytokines such as TNF-α, IL-6, and iNOS. The results also illustrated that MRS treatment diminished apoptosis in the hippocampal CA1 region , reduced the expression of apoptosis-associated proteins Bax and cleaved caspase9, and increased Bcl-2 expression, as well as inhibited the expression of endoplasmic reticulum (ER) stress pathway-related proteins GRP78, ATF4, and CHOP. Further findings showed that MRS treatment significantly attenuated hippocampal ROS and MDA levels and increased GSH and SOD antioxidant factor levels, which indicated that MRS treatment could inhibit oxidative stress. Our results suggest that MRS exerts a protective effect against CA/CPR brain injury, by inhibiting oxidative stress, microglial activation-induced inflammatory responses, and ER stress-mediated apoptosis.

scholarly journals Evaluation of arginase activity, nitric oxide and oxidative stress status in sheep with contagious agalactia

2017 ◽  
Vol 65 (3) ◽  
pp. 394-401 ◽  
Author(s):  
Basak Hanedan ◽  
Akin Kirbas ◽  
Fatih Mehmet Kandemir ◽  
Mustafa Sinan Aktas ◽  
Ahmet Yildiz
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Proinflammatory Cytokine ◽  
Arginase Activity ◽  
Cytokine Release ◽  
Contagious Agalactia ◽  
Oxidative Stress Status ◽  
Healthy Sheep ◽  
Total Antioxidant ◽  
And Oxidative Stress

It is known that inflammatory organ damages due to various agents, such as microorganisms including mycoplasmas, lead to oxidative stress. Nitric oxide (NO) functions as an antimicrobial agent, and arginase decreases proinflammatory cytokine release. There are very few studies on arginase activity, NO level and oxidative stress status in mycoplasmal infections. Therefore, the aim of this study was to evaluate erythrocyte arginase activity, plasma NO level and oxidative stress status in sheep with contagious agalactia. The study material consisted of 10 healthy sheep and 14 sheep with contagious agalactia characterised by mastitis, arthritis and keratoconjunctivitis. Erythrocyte arginase activity, plasma NO, malondialdehyde (MDA), total oxidant capacity (TOC) and total antioxidant capacity (TAC) levels were measured. Significant decreases in erythrocyte arginase activity and plasma TAC level (P < 0.001), and significant increases in plasma NO, MDA and TOC levels (P < 0.001) were found in the diseased sheep as compared with the healthy animals. This study suggests that contagious agalactia may cause oxidative stress due to increased plasma MDA and TOC levels and decreased plasma TAC levels, and that the decrease in erythrocyte arginase activity and increase in plasma NO level may contribute to the elimination of mycoplasmal agents causing contagious agalactia.

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