Oxide Stress Research Articles

Traffic-related air pollution, chronic stress, and changes in exhaled nitric oxide and lung function among a panel of children with asthma living in an underresourced community

We examined associations between short-term exposure to traffic-related air pollutants (TRAP) and airway inflammation and lung function in children with asthma, and whether these associations are modified by chronic psychological stress. Residents of underresourced port-adjacent communities in New Jersey were concerned about the cumulative impacts of exposure to TRAP, particularly diesel-engine truck emissions, and stress on exacerbation of asthma among children. Children with asthma aged 9–14 (n = 35) were recruited from non-smoking households. We measured each participant's (1) continuous personal exposure to black carbon (BC, a surrogate of TRAP) at 1-min intervals, (2) 24-h integrated personal exposure to nitrogen dioxide (NO2), (3) daily fractional exhaled nitric oxide (FeNO), and (4) lung function for up to 30 consecutive days. Personal BC was recorded by micro-aethalometers. We measured daily FeNO using the NIOX MINO, forced expiratory volume in one second (FEV1), and forced vital capacity (FVC) using Easy One Frontline spirometers. Chronic stress was measured with the UCLA Life Stress Interview for Children. The association was examined using linear mixed-effect models. In the fully adjusted model, an interquartile range (IQR) increase in BC at lag 0–6 h before the FeNO measurement was associated with 8 % (95 % CI: 3 % - 12 %) increase in FeNO, whereas an IQR increase in BC at lag 7–12 h and lag 0–24 h were associated with 6 % (95 % CI: 2 % - 11 %) and 7 % (2 % - 12 %) FeNO increases, respectively. There were no significant lung function changes per IQR increase in BC. No interactions were observed between chronic stress and BC on FeNO. Chronic stress was negatively associated with individual average FeNO levels. Our findings suggest that higher levels of BC exposure within the prior 24 h increased airway inflammation levels in children with asthma, with the strongest effect observed within the first 6 h.

The contribution of DNA repair pathways to Staphylococcus aureus fitness and fidelity during nitric oxide stress.

Pathogenic bacteria must evolve various mechanisms in order to evade the host immune response that they are infecting. One aspect of the primary host immune response to an infection is the production of an inflammatory effector component, nitric oxide (NO⋅). Staphylococcus aureus has uniquely evolved a diverse array of strategies to circumvent the inhibitory activity of nitric oxide. One such mechanism by which S. aureus has evolved allows the pathogen to survive and maintain its genomic integrity in this environment. For instance, here, our results suggest that S. aureus employs several DNA repair pathways to ensure replicative fitness and fidelity under NO⋅ stress. Thus, our study presents evidence of an additional strategy that allows S. aureus to evade the cytotoxic effects of host NO⋅.

Activation of multiple stress responses in Staphylococcus aureus substantially lowers the minimal inhibitory concentration when combining two novel antibiotic drug candidates.

The past few decades have been plagued by an increasing number of infections caused by antibiotic resistant bacteria. To mitigate the rise in untreatable infections, we need new antibiotics with novel targets and drug combinations that reduce resistance development. The novel β-clamp targeting antimicrobial peptide BTP-001 was recently shown to have a strong additive effect in combination with the halogenated pyrrolopyrimidine JK-274. In this study, the molecular basis for this effect was examined by a comprehensive proteomic and metabolomic study of the individual and combined effects on Staphylococcus aureus. We found that JK-274 reduced activation of several TCA cycle enzymes, likely via increasing the cellular nitric oxide stress, and BTP-001 induced oxidative stress in addition to inhibiting replication, translation, and DNA repair processes. Analysis indicated that several proteins linked to stress were only activated in the combination and not in the single treatments. These results suggest that the strong additive effect is due to the activation of multiple stress responses that can only be triggered by the combined effect of the individual mechanisms. Importantly, the combination dose required to eradicate S. aureus was well tolerated and did not affect cell viability of immortalized human keratinocyte cells, suggesting a species-specific response. Our findings demonstrate the potential of JK-274 and BTP-001 as antibiotic drug candidates and warrant further studies.

Pomegranate-Derived Exosome-Like Nanovesicles Alleviate Binge Alcohol-Induced Leaky Gut and Liver Injury.

Alcoholic liver disease (ALD) is damage to the liver and mainly caused by binge alcohol. ALD have decreased junctional protein expression and modulated intestinal permeability. We investigated whether plant-releasing exosome-like nanovesicles can prevent liver damage and leaky gut from binge alcohol. In this study, we characterized the exosome-like nanovesicles from pomegranate juice and confirmed the round shape of a lipid bilayer. After 14 days of pomegranate-derived exosome-like nanovesicle (PNVs) pretreatment, binge alcohol (6 g/kg/dose) was administered to mice three times orally every 12 h. Exposure to binge alcohol increased levels of oxidative and nitric oxide stress marker proteins such as CYP2E1, 3-Nitrotyrosine, and inducible nitric oxide synthase in both liver and gut damage. Also, binge alcohol significantly elevated the plasma endotoxemia, inflammatory fatty liver, and leaky gut. However, PNVs reduced the oxidative stress and apoptosis marker proteins and prevented the leaky gut and endotoxemia. Markedly, PNV treatment significantly prevented a decrease in the amount of intestinal junctional proteins and an increase in leaky gut in mice exposed to alcohol. These results showed that PNVs can prevent leaky gut and liver damage caused by binge alcohol and suggest that it may be useful hepatoprotective or intestinal protective agents for the first time.

Amino acids, post-translational modifications, nitric oxide, and oxidative stress in serum and urine of long COVID and ex COVID human subjects

In this study, we investigated the status of amino acids, their post-translational modifications (PTM), major nitric oxide (NO) metabolites and of malondialdehyde (MDA) as a biomarker of oxidative stress in serum and urine samples of long COVID (LoCo, n = 124) and ex COVID (ExCo, n = 24) human subjects collected in 2022. Amino acids and metabolites were measured by gas chromatography–mass spectrometry (GC–MS) methods using stable-isotope labelled analogs as internal standards. There were no differences with respect to circulating and excretory arginine and asymmetric dimethylarginine (ADMA). LoCo participants excreted higher amounts of guanidino acetate than ExCo participants (17.8 ± 10.4 µM/mM vs. 12.6 ± 8.86 µM/mM, P = 0.005). By contrast, LoCo participants excreted lower amounts of the advanced glycation end-product (AGE) NG-carboxyethylarginine (CEA) than ExCo participants did (0.675 ± 0.781 µM/mM vs. 1.16 ± 2.04 µM/mM, P = 0.0326). The serum concentrations of MDA did not differ between the groups, indicating no elevated oxidative stress in LoCo or ExCo. The serum concentration of nitrite was lower in LoCo compared to ExCo (1.96 ± 0.92 µM vs. 2.56 ± 1.08 µM; AUC, 0.718), suggesting altered NO synthesis in the endothelium. The serum concentration of nitrite correlated inversely with the symptom anxiety (r = − 0.293, P = 0.0003). The creatinine-corrected urinary excretion of Lys and its metabolite L-5-hydroxy-Lys correlated positively with COVID toes (r = 0.306, P = 0.00027) and sore throat (r = 0.302, P = 0.0003). Our results suggest that amino acid metabolism, PTM and oxidative stress are not severely affected in long COVID. LoCo participants may have a lower circulating NO reservoir than ExCo.

Decoupling the roles of grain boundary oxidation and stress in IASCC of neutron-irradiated 304L stainless steel

Irradiation assisted stress corrosion cracking (IASCC) is known to be a combination of applied stress, and a corrosive environment in irradiated materials, but an appropriate understanding of how each of these components affects cracking is not yet clear. In this work, we isolate the role of grain boundary (GB) oxidation in IASCC. For this purpose, solution-annealed 304L stainless steel irradiated in reactor to 5.4 or 69 dpa was studied using a miniaturized four-point bend technique. Two modes of bend tests were conducted; straining in simulated pressurized water reactor primary water (PW) at 320 °C in an incremental manner, and pre-oxidation in PW at 320 °C without application of stress followed by dynamic straining in purified Ar at the same temperature until crack initiation. Exposure of the 5.4 dpa sample for 210 h in high temperature water initiated cracks in Ar at 60% of the yield stress (0.6YS), whereas the companion sample of the same dose exposed for 1010 h cracked in Ar at 0.5YS. The long-term exposure in water led to GB oxidation that ultimately lowered the crack initiation stress. Dynamic straining in water resulted in larger crack lengths and greater crack depths indicating stress accelerated oxidation and cracking. Dislocation pile-ups at dislocation channel-grain boundary sites provide an amplification of the applied stress to a level consistent with the fracture stress of the grain boundary oxide, providing an explanation for IASCC that occurs at applied stresses well below the irradiated yield stress of the alloy. There was no evidence of cracking upon straining of an unoxidized 69 dpa sample in Ar to well above yield, confirming that the irradiated state is not inherently susceptible to intergranular (IG) cracking and that oxidized GBs are responsible for initiation of IG cracking.

The aerotaxis of Dictyostelium discoideum is independent of mitochondria, nitric oxide and oxidative stress.

Spatial and temporal variations of oxygen environments affect the behaviors of various cells and are involved in physiological and pathological events. Our previous studies with Dictyostelium discoideum as a model of cell motility have demonstrated that aerotaxis toward an oxygen-rich region occurs below 2% O2. However, while the aerotaxis of Dictyostelium seems to be an effective strategy to search for what is essential for survival, the mechanism underlying this phenomenon is still largely unclear. One hypothesis is that an oxygen concentration gradient generates a secondary oxidative stress gradient that would direct cell migration towards higher oxygen concentration. Such mechanism was inferred but not fully demonstrated to explain the aerotaxis of human tumor cells. Here, we investigated the role on aerotaxis of flavohemoglobins, proteins that can both act as potential oxygen sensors and modulators of nitric oxide and oxidative stress. The migratory behaviors of Dictyostelium cells were observed under both self-generated and imposed oxygen gradients. Furthermore, their changes by chemicals generating or preventing oxidative stress were tested. The trajectories of the cells were then analyzed through time-lapse phase-contrast microscopic images. The results indicate that both oxidative and nitrosative stresses are not involved in the aerotaxis of Dictyostelium but cause cytotoxic effects that are enhanced upon hypoxia.

Zataria multiflora and its constituent, carvacrol, counteract sepsis-induced aortic and cardiac toxicity in rat: Involvement of nitric oxide and oxidative stress.

Zataria multiflora and carvacrol showed various pharmacological properties including anti-inflammatory and anti-oxidant effects. However, up to now no studies have explored its potential benefits in ameliorating sepsis-induced aortic and cardiac injury. Thus, this study aimed to investigate the effects of Z. multiflora and carvacrol on nitric oxide (NO) and oxidative stress indicators in lipopolysaccharide (LPS)-induced aortic and cardiac injury. Adult male Wistar rats were assigned to: Control, lipopolysaccharide (LPS) (1 mg/kg, intraperitoneal (i.p.)), and Z. multiflora hydro-ethanolic extract (ZME, 50-200 mg/kg, oral)- and carvacrol (25-100 mg/kg, oral)-treated groups. LPS was injected daily for 14 days. Treatment with ZME and carvacrol started 3 days before LPS administration and treatment continued during LPS administration. At the end of the study, the levels of malondialdehyde (MDA), NO, thiols, and antioxidant enzymes were evaluated. Our findings showed a significant reduction in the levels of superoxide dismutase (SOD), catalase (CAT), and thiols in the LPS group, which were restored by ZME and carvacrol. Furthermore, ZME and carvacrol decreased MDA and NO in cardiac and aortic tissues of LPS-injected rats. The results suggest protective effects of ZME and carvacrol on LPS-induced cardiovascular injury via improved redox hemostasis and attenuated NO production. However, additional studies are needed to elucidate the effects of ZME and its constituents on inflammatory responses mediated by LPS.

Numerical simulation of the residual stress and failure probability of solid oxide fuel cells with nonplanar cathode–electrolyte interfaces

ABSTRACT The actual surface of solid oxide fuel cells exhibits a fluctuating nature. In this study, the residual stresses and failure probability of nonplanar interfaces with different waveforms and wavelengths were investigated using a cosine interface approximation technique to simulate the actual cathode – electrolyte interface. Results showed that the electrolyte was subjected to compressive stresses with a maximum value at the trough. During cell preparation, the anode underwent conversion from an oxidized state to a reduced state, reducing residual stress in the electrode. Increasing the amplitude exerted a significantly greater effect on stress change than decreasing it. When the wavelength is longer, the stress fluctuation is lower. During anode reduction, the cathode reached the highest probability of failure and was damaged when the nickel oxide content exceeded 55%. A minimum anode thickness of 0.6 mm ensured anode stability.

GlfT1 down-regulation affects Mycobacterium tuberculosis biofilm formation and its in-vitro and in-vivo survival

Mycobacterial galactan biosynthesis is critical for cell viability and growth, therefore an effort was made to study galactofuranosyl transferase 1, encoded by MRA_3822 in Mycobacterium tuberculosis H37Ra (Mtb-Ra). Galactofuranosyl transferases are involved in the biosynthesis of mycobacterial cell wall galactan chain and have been shown to be essential for in-vitro growth of Mycobacterium tuberculosis. In Mtb-Ra and Mycobacterium tuberculosis H37Rv (Mtb-Rv), two galactofuranosyl transferases are present, GlfT1 acts as initiator of galactan biosynthesis and GlfT2 continues with the subsequent polymerization events. GlfT2 has been well studied however GlfT1 inhibition/down-regulation and its effect on mycobacterial survival fitness has not been evaluated. To study the Mtb-Ra survival after GlfT1 silencing, Mtb-Ra knockdown and complemented strains were developed. In this study we show that GlfT1 down-regulation leads to increased susceptibility to ethambutol. Expression of glfT1 was up-regulated in the presence of ethambutol, and also in the presence of oxidative and nitrosative stress and upon exposure to low pH. Also, reduced biofilm formation, increased accumulation of ethidium bromide, and reduced tolerance to peroxide, nitric oxide and acid stress, were observed. The present study also demonstrates that GlfT1 down-regulation leads to reduced survival of Mtb-Ra in macrophages and in mice.

FGFR2 modulates the Akt/Nrf2/ARE signaling pathway to improve angiotensin II-induced hypertension-related endothelial dysfunction

ABSTRACT Background Fibroblast growth factor receptor (FGFR)2 expression was decreased in hypertension patients while its role in hypertension was not explored. This experiment aimed to investigate the expression ofFGFR2 in angiotensin II (Ang II)-induced human umbilical vein endothelial cells (HUVECs) and the role of FGFR2 in improving AngII-induced hypertension-related endothelial dysfunction. Methods AngII-induced HUVECs simulated the hypertension model in vitro. The expression of FGFR2 in Ang II-induced HUVECs and transfected HUVECswas detected by RT-qPCR and western blot. The viability, apoptosis, migration and tube formation ability of Ang II-induced HUVECs were analyzed by Methyl Thiazolyl Tetrazolium (MTT) assay, flow cytometry analysis, wound healing assay and tube formation assay.Detectionof lactate dehydrogenase (LDH), caspase 3, Nitric Oxide (NO) and oxidative stress levels was conducted by assay kits and reactive oxygen species (ROS) level was detected by DCFH-DA assay. The expression of apoptosis-related proteins, protein kinase B(Akt)/nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway-related proteins, phospho(p)-endothelial nitric oxide synthase (eNOS) and eNOS was determined by western blot. Results The expression of FGFR2 was decreased in Ang II-induced HUVECs. FGFR2overexpression increased viability, suppressed apoptosis and oxidative stress, and improve endothelial dysfunction of AngII-induced HUVECs through activating the Akt/Nrf2/ARE signaling pathway. MK-2206 (Akt inhibitor) could weaken the effect of FGFR2overexpression to reduce viability, promote apoptosis and oxidative stress, and aggravate endothelial dysfunction of Ang II-inducedHUVECs. Conclusion Inconclusion, FGFR2activated the Akt/Nrf2/ARE signaling pathway to improve AngII-induced hypertension-related endothelial dysfunction.

The involvement of CdhR in Porphyromonas gingivalis during nitric oxide stress.

Porphyromonas gingivalis, the causative agent of adult periodontitis, must gain resistance to frequent oxidative and nitric oxide (NO) stress attacks from immune cells in the periodontal pocket to survive. Previously, we found that, in the wild-type and under NO stress, the expression of PG1237 (CdhR), the gene encoding for a putative LuxR transcriptional regulator previously called community development and hemin regulator (CdhR), was upregulated 7.7-fold, and its adjacent gene PG1236 11.9-fold. Isogenic mutants P. gingivalis FLL457 (ΔCdhR::ermF), FLL458 (ΔPG1236::ermF), and FLL459 (ΔPG1236-CdhR::ermF) were made by allelic exchange mutagenesis to determine the involvement of these genes in P. gingivalis W83 NO stress resistance. The mutants were black pigmented and β hemolytic and their gingipain activities varied with strains. FLL457 and FLL459 mutants were more sensitive to NO compared to the wild type, and complementation restored NO sensitivity to that of the wild type. DNA microarray analysis of FLL457 showed that approximately 2% of the genes were upregulated and over 1% of the genes downregulated under NO stress conditions compared to the wild type. Transcriptome analysis of FLL458 and FLL459 under NO stress showed differences in their modulation patterns. Some similarities were also noticed between all mutants. The PG1236-CdhR gene cluster revealed increased expression under NO stress and may be part of the same transcriptional unit. Recombinant CdhR showed binding activity to the predicted promoter regions of PG1459 and PG0495. Taken together, the data indicate that CdhR may play a role in NO stress resistance and be involved in a regulatory network in P. gingivalis.

Hepatic effect of subacute Fe2 O3 nanoparticles exposure in Sprague-Dawley rats by LC-MS/MS based lipidomics.

Fe2 O3 nanoparticles (Fe2 O3 NPs) are one of the components of food additives numbered E172 and have been widely used as food pigments to color sweets. Although a large number of studies have reported that Fe2 O3 NPs could induce hepatotoxicity, the pathogenesis is still unclear, especially the subacute effects on the metabolic network after oral exposure. Therefore, it is necessary to define a highly sensitive strategy to investigate the potential effects of Fe2 O3 NPs and the mechanism. In this study, an animal experiment showed that Fe2 O3 NPs had no obvious toxic effects on body weight, histopathology and oxide stress. In order to further investigate the potential effects of Fe2 O3 NPs in vivo, a more sensitive LC-MS/MS-based lipidomic study was performed. The results of multivariate statistical analysis and western blot analysis showed that Fe2 O3 NP exposure significantly affects the hepatic glycerophospholipid metabolism, decreasing triacylglycerol, diglyceride, lysophosphatidylethanolamine and free fatty acids, and increasing phosphatidylcholine, lysophosphatidylinositol and coenzyme Q9. These data provide further insight into the hepatic subacute effects of Fe2 O3 NPs obtained by conventional toxicology methods.

The relationship between salivary alpha-amylase, nitric oxide, pain and anxiety-induced stress in patients during dental treatment.

Pain and anxiety are the most reported negative effect of orthodontic treatment which can influence the quality of life and are responsible for the discontinuation of treatment. These unpleasant experiences raise the stress levels reflected by the increase in the concentration of salivary alpha-amylase and nitric oxide. These can be assessed through various subjective methods which have limited value as it depends on the patient's honesty, assessing whether using objective methods are reliable. To assess pain and anxiety-induced stress levels using both physiological (Salivary alpha-amylase and Salivary nitric oxide) and psychological testing instruments (Visual analog scale and State Trait Anxiety Inventory Y6) during the initial phases of fixed orthodontic treatment. A total of 30 patients were included. Pain and anxiety instruments were applied and saliva samples were collected from patients before and after separator placement, before and 48 h after archwire insertion and 1 month after archwire insertion. The mean values of alpha-amylase (235.3600), nitric oxide levels (2.060) and pain scores (7.8667) were higher 48 h after archwire insertion (T3) which are statistically significant, P = 0.00. Anxiety scores (57.7000) were high before separator placement (T0). No statistically significant correlation was found among pain and alpha-amylase, anxiety and nitric oxide levels. Initial alignment phases of fixed orthodontic treatment affect patients' anxiety and stress levels. The findings could be a result of the psychological stress due to procedures in the initial phases of the treatment.

Oxide growth and stress evolution underneath cracked environmental barrier coatings

SiC composites at elevated temperatures are prone to oxidation, prompting the use of environmental barrier coatings to limit or prevent the ingress of oxidants. Cracks in such coatings can provide fast diffusion pathways that can lead to accelerated local oxide growth. The localized oxide confined at the tip of such features generates significant stress due to the large molar volume change associated with converting SiC to SiO2. In this work, a multi-physics computational framework is used to simulate the evolution of such internal oxide domains; the framework integrates analyses of oxidant transport, oxide growth (domain evolution) in dry air environments and stress evolution mitigated by creep. Significant insights regarding oxidation-driven damage are obtained from a broad parametric study involving the crack opening, the effective diffusivity of the coating, the crack spacing and the magnitude of applied loads. (i) Oxide growth at the tip of the crack is comparable to that of a bare surface; even very narrow open channels lead to rapid, localized oxidation. (ii) Coatings with low diffusivity produce highly confined oxide ‘bubbles’ at the tip of the crack; confinement produces high compressive stresses in the oxide and significant tensile stresses in the surrounding material. Stresses along the coating/substrate interface and in the substrate beneath the bubble can be 2–7 times those arising from mechanical loading alone, promoting coating decohesion and substrate cracking. (iii) Significant applied stress reduces high hydrostatic stresses in the oxide and mitigate the stress elevation associated with local oxidation. The paper concludes with a brief discussion of the implications of these observations for damage mechanisms occurring at elevated temperature, and indicate the importance of further study of the impact of wet environments and different oxide compositions.

Investigation of the effect of Sugammadex on glutamate-induced neurotoxicity in C6 cell line and the roles played by nitric oxide and oxidative stress pathways.

This experiment was intended to evaluate the effect of sugammadex on the cytotoxicity induced by glutamate, involving the nitric oxide and oxidative stress pathways. C6 glioma cells were used in the study. Glutamate was given to cells in the glutamate group for 24 h. Sugammadex at different concentrations was given to cells in the sugammadex group for 24 h. Cells in the sugammadex + glutamate group were pre-treated with sugammadex at various concentrations for 1 h and then exposed to glutamate for 24 h. XTT assay was used to assess the cell viability. The levels of nitric oxide (NO), neuronal nitric oxide synthase (nNOS), total antioxidant (TAS), and total oxidant (TOS) in the cells were calculated using commercial kits. Apoptosis was detected by TUNEL assay. Sugammadex at concentrations of 50 and 100 μg/mL significantly enhanced the cell viability in C6 cells after the cytotoxicity induced by glutamate (p < 0.001). Moreover, sugammadex considerably decreased the levels of nNOS NO and TOS and the number of apoptotic cells and increased the level of TAS (p < 0.001). Sugammadex has protective and antioxidant properties on cytotoxicity and could be an effective supplement for neurodegenerative diseases such as Alzheimer and Parkinson if further research in vivo supports this claim.

Spallation mechanism of thermal barrier coatings with real interface morphology considering growth and thermal stresses based on fracture phase field

The interface of atmospheric plasma spray (APS) thermal barrier coatings (TBCs) is extremely rough and uneven, causing extremely complicated laws in thermally grown oxide (TGO) growth, stress distribution and evolution, as well as crack initiation and expansion. In this paper, a fracture phase field theory of TBCs interfaces with considerations of growth and thermal stresses is established. A two-dimensional geometric model of APS TBCs was constructed based on the real interface morphology. Next, the TGO growth laws and interface spallation mechanism during the service of TBCs were studied through numerical simulation and experiment. Results demonstrated that the TGO growth rate at the convex position on the interface is higher than those at other positions, especially at the local convex positions. TGO at the left and right sides of concave positions approach continuously with oxidisation of the interface, causing the TGO to wrinkle and the interface to become rougher. With an increase in TGO thickness, stresses in the TGO at peak areas perpendicular to the interface increase significantly and their maximum reaches to 1.58 GPa. Interface cracks initiated in peak areas around the TGO/BC interface at 877 h, and then formed in flat positions in the TGO at 912 h as well as valley areas around the TGO/TC interface at 928 h. Final, TBCs failed at 959 h due to the coalescence of these cracks. All four types of interface cracks could be found in the simulation results.

Synergistic effect of ellagic acid and gabapentin in a rat model of neuropathic pain.

Neuropathic pain is a subtype of chronic pain characterized by a primary lesion or dysfunction of the peripheral or central nervous system. The current pain management of neuropathic pain is inadequate and needs new medications. We studied the effects of 14 days of intraperitoneal ellagic acid (EA) and gabapentin administration in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the right sciatic nerve. Rats were divided into six groups: (1) control, (2) CCI, (3) CCI + EA (50mg/kg), 4) CCI + EA (100mg/kg), 5) CCI + gabapentin (100mg/kg), and 6) CCI + EA (100mg/kg) + gabapentin (100mg/kg). Behavioral tests, including mechanical allodynia, cold allodynia, and thermal hyperalgesia, were conducted on days - 1(pre-operation), 7, and 14 post-CCI. In addition, at day 14 post-CCI, spinal cord segments were collected to measure the expression of inflammatory markers, including tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), and oxidative stress markers, including malondialdehyde (MDA) and thiol. CCI increased mechanical allodynia, cold allodynia, and thermal hyperalgesia in rats which were reduced by treatment with EA (50 or 100mg/kg), gabapentin, or their combination. CCI increased TNF-α, NO, and MDA levels and decreased thiol content in the spinal cord, which all were reverted by administration of EA (50 or 100mg/kg), gabapentin, or their combination. This is the first report on ellagic acid's ameliorative effect in rats' CCI-induced neuropathic pain. This effect can be attributed to its anti-oxidative and anti-inflammatory, thus making it potentially useful as an adjuvant to conventional treatment.

The effects of phytosomal curcumin supplementation on clinical symptoms, and inflammatory and oxidative stress biomarkers in patients with migraine: A protocol for a randomized double-blind placebo-controlled trial.

Migraine is one of the most common diseases. Curcumin with anti-oxidative and anti-neuroinflammatory properties might have beneficial effects in migraine patients. This study will be conducted to evaluate the effects of a phytosomal preparation of curcumin on clinical signs, oxidative stress, and inflammatory parameters in patients with migraine. This is a randomized, double-blind, placebo-controlled, clinical trial in which, 60 patients with migraine will be assigned to receive a daily dose of 250 mg of phytosomal curcumin for 8 weeks (intervention group) or 250 mg maltodextrin as a placebo for the same duration (control group). Before and after the study, frequency, duration, and severity of the attacks, quality of life and sleep, mood status, high-sensitivity C-reactive protein (hs-CRP), Nitric Oxide (NO), and oxidative stress factors will be measured. It seems that phytosomal formulation of curcumin (a solid dispersion preparation of curcumin with phosphatidylserine) with high bioavailability, can cross the blood-brain barrier (BBB) and result in decreased neuroinflammation, oxidative stress, and neurotoxicity. This way, phytosomal curcumin might lead to reduction of headaches and other complications of migraine and increase the quality of life of patients with migraine.

The effects of handball and waterpolo training on blood nitric oxide and oxidative stress levels

Objective: Nitric oxide (NO) is a gas that has vasodilatory, antioxidant and metabolic regulatory properties. Both NO and oxidative stress (OS) are risk factors for atherosclerosis (AS). These properties of NO, therefore play a critical role in training adaptations. Handball and water polo are team sports requiring aerobic and anaerobic energy. However, since they are practised in different environments, their effects on blood NO and OS levels may be different. Therefore, this study aimed to compare the effects of these two team sports on blood NO and OS levels. Material and Methods: Male handball players (HG, n=14), water polo players (WPG, n=12) and a control group (CG, n=13) of sedentary players participated in this study. Physical and physiological measurements, including critical velocity of the participants were made. The participants' fasting serum NO and OS indicators, and total antioxidant/oxidant status (TAS/TOS) were determined. Results: TAS levels of HG and WPG were significantly lower than those of the control group (p&lt;0.05, p&lt;0.01), whereas their NO levels were higher than those of CG (19.5% and 25.7% respectively, p&gt;0.05). No significant difference was present for NO between HG and WPG. A significant negative correlation was present between CV and serum NO level, and there was a positive correlation between maximal 1500 m running time and NO for handball players. Conclusions: The findings of the study reveal that although training caused a significant decrease in antioxidant capacity in two team sports athletes, serum NO levels improved, thereby contributing to cardiovascular health. NO may harm aerobic endurance performance, but it had a beneficial effect on anaerobic power in the handball group, and none for water polo players.