PWE-056 A compensatory anti-inflammatory response syndrome triggered by neutrophil-induced oxidative stress is associated with chronic low grade hepatic encephalopathy in patients with advanced cirrhosis

Inflammation and oxidative stress are part of the complex biological responses of body tissues to harmful stimuli. In recent years, due to the increased understanding that oxidative stress is implicated in several diseases, pharmaceutical industries have invested in the research and development of new antioxidant compounds, especially from marine environment sources. Marine seaweeds have shown the presence of many bioactive secondary metabolites, with great potentialities from both the nutraceutical and the biomedical point of view. In this study, 50%-ethanolic and DMSO extracts from the species C. amentacea var. stricta were obtained for the first time from seaweeds collected in the Ligurian Sea (north-western Mediterranean). The bioactive properties of these extracts were then investigated, in terms of quantification of specific antioxidant activities by relevant ROS scavenging spectrophotometric tests, and of anti-inflammatory properties in LPS-stimulated macrophages by evaluation of inhibition of inflammatory cytokines and mediators. The data obtained in this study demonstrate a strong anti-inflammatory effect of both C. amentacea extracts (DMSO and ethanolic). The extracts showed a very low grade of toxicity on RAW 264.7 macrophages and L929 fibroblasts and a plethora of antioxidant and anti-inflammatory effects that were for the first time thoroughly investigated. The two extracts were able to scavenge OH and NO radicals (OH EC50 between 392 and 454 μg/mL; NO EC50 between 546 and 1293 μg/mL), to partially rescue H2O2-induced RAW 264.7 macrophages cell death, to abate intracellular ROS production in H2O2-stimulated macrophages and fibroblasts and to strongly inhibit LPS-induced inflammatory mediators, such as NO production and IL-1α, IL-6, cyclooxygenase-2 and inducible NO synthase gene expression in RAW 264.7 macrophages. These results pave the way, for the future use of C. amentacea metabolites, as an example, as antioxidant food additives in antiaging formulations as well as in cosmetic lenitive lotions for inflamed and/or damaged skin.

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Modulation of the inflammatory response to LPS by the recruitment and activation of brown and brite adipocytes in mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00279.2020 ◽

2020 ◽

Vol 319 (5) ◽

pp. E912-E922

Author(s):

Patrick Munro ◽

Océane Dufies ◽

Samah Rekima ◽

Agnès Loubat ◽

Christophe Duranton ◽

...

Keyword(s):

Adipose Tissue ◽

Inflammatory Response ◽

Low Grade ◽

Inflammatory Phenotype ◽

Anti Inflammatory ◽

And Function

Recruitment and activation of brown and brite adipocytes in the adipose tissue of mice lead to a local low-grade anti-inflammatory phenotype in response to acute endotoxemia without alteration of adipocyte phenotype and function.

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PGC-1α, Inflammation, and Oxidative Stress: An Integrative View in Metabolism

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/1452696 ◽

2020 ◽

Vol 2020 ◽

pp. 1-20 ◽

Cited By ~ 21

Author(s):

Sergio Rius-Pérez ◽

Isabel Torres-Cuevas ◽

Iván Millán ◽

Ángel L. Ortega ◽

Salvador Pérez

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Metabolic Syndrome ◽

Inflammatory Response ◽

Reactive Oxygen ◽

High Energy ◽

Low Grade ◽

Oxygen Species ◽

Antioxidant Genes ◽

Integrative View

Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α is a transcriptional coactivator described as a master regulator of mitochondrial biogenesis and function, including oxidative phosphorylation and reactive oxygen species detoxification. PGC-1α is highly expressed in tissues with high energy demands, and it is clearly associated with the pathogenesis of metabolic syndrome and its principal complications including obesity, type 2 diabetes mellitus, cardiovascular disease, and hepatic steatosis. We herein review the molecular pathways regulated by PGC-1α, which connect oxidative stress and mitochondrial metabolism with inflammatory response and metabolic syndrome. PGC-1α regulates the expression of mitochondrial antioxidant genes, including manganese superoxide dismutase, catalase, peroxiredoxin 3 and 5, uncoupling protein 2, thioredoxin 2, and thioredoxin reductase and thus prevents oxidative injury and mitochondrial dysfunction. Dysregulation of PGC-1α alters redox homeostasis in cells and exacerbates inflammatory response, which is commonly accompanied by metabolic disturbances. During inflammation, low levels of PGC-1α downregulate mitochondrial antioxidant gene expression, induce oxidative stress, and promote nuclear factor kappa B activation. In metabolic syndrome, which is characterized by a chronic low grade of inflammation, PGC-1α dysregulation modifies the metabolic properties of tissues by altering mitochondrial function and promoting reactive oxygen species accumulation. In conclusion, PGC-1α acts as an essential node connecting metabolic regulation, redox control, and inflammatory pathways, and it is an interesting therapeutic target that may have significant benefits for a number of metabolic diseases.

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Oxidative stress and hippocampus in a low-grade hepatic encephalopathy model: protective effects of curcumin

Hepatology Research ◽

10.1111/j.1872-034x.2008.00377.x ◽

2008 ◽

Vol 38 (11) ◽

pp. 1148-1153 ◽

Cited By ~ 10

Author(s):

Diego Martín Roselló ◽

Karina Balestrasse ◽

Carlos Coll ◽

Sebastian Coll ◽

Silvina Tallis ◽

...

Keyword(s):

Oxidative Stress ◽

Hepatic Encephalopathy ◽

Low Grade ◽

Protective Effects

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Dietary Spray-Dried Porcine Plasma Prevents Cognitive Decline in Senescent Mice and Reduces Neuroinflammation and Oxidative Stress

Journal of Nutrition ◽

10.1093/jn/nxz239 ◽

2019 ◽

Cited By ~ 3

Author(s):

Alba Garcia-Just ◽

Lluïsa Miró ◽

Anna Pérez-Bosque ◽

Concepció Amat ◽

Javier Polo ◽

...

Keyword(s):

Oxidative Stress ◽

Cognitive Decline ◽

Brain Tissue ◽

Cognitive Performance ◽

Dietary Supplementation ◽

Low Grade ◽

Anti Inflammatory ◽

Samp8 Mice ◽

And Oxidative Stress ◽

Spray Dried

ABSTRACT Background Aging is characterized by chronic, low-grade inflammation that correlates with cognitive decline. Dietary supplementation with spray-dried porcine plasma (SDP) reduces immune activation in rodent models of inflammation and aging. Objective We investigated whether the anti-inflammatory properties of SDP could ameliorate age-related cognitive deterioration and preserve brain homeostasis in an aging mouse model of senescence. Methods Male senescence-accelerated prone 8 (SAMP8) mice were used. In Experiment 1, cognitive performance (n = 10–14 mice/group) was analyzed by the novel object recognition test in 2-mo-old mice (2M group) and in mice fed a control diet or a diet supplemented with 8% SDP for 2 (4M-CTL and 4M-SDP groups) and 4 mo (6M-CTL and 6M-SDP groups). In Experiment 2, the permeability of the blood–brain barrier and junctional proteins in brain tissue was assessed, as well as synaptic density, oxidative stress markers, and inflammatory genes and proteins in mice from the 2M, 6M-CTL, and 6M-SDP groups ( n = 5–11). Statistical analyses included one-factor ANOVA followed by Fisher's posthoc test. Results 6M-SDP mice had better cognitive performance than 6M-CTL mice in both short-term (P = 0.024) and long-term (P = 0.017) memory tests. In brain tissue, 6M-SDP mice showed reduced brain capillary permeability (P = 0.034) and increased ZO1 and E-cadherin expression (both P <0.04) compared with 6M-CTL mice. SDP also prevented the NFκB activation observed in 6M-CTL mice (P = 0.002) and reduced Il6 expression and hydrogen peroxide concentration (both P <0.03) observed in 6M-CTL mice. SDP also increased the concentration of IL10 (P = 0.027), an anti-inflammatory cytokine correlated with memory preservation. Conclusions In senescent SAMP8 mice, dietary supplementation with SDP attenuated cognitive decline and prevented changes in brain markers of neuroinflammation and oxidative stress.

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Sorghum genotype may reduce low-grade inflammatory response and oxidative stress and maintains jejunum morphology of rats fed a hyperlipidic diet

Food Research International ◽

10.1016/j.foodres.2012.07.029 ◽

2012 ◽

Vol 49 (1) ◽

pp. 553-559 ◽

Cited By ~ 40

Author(s):

Érica Aguiar Moraes ◽

Dorina Isabel Gomes Natal ◽

Valéria Aparecida Vieira Queiroz ◽

Robert Eugene Schaffert ◽

Paulo Roberto Cecon ◽

...

Keyword(s):

Oxidative Stress ◽

Inflammatory Response ◽

Low Grade ◽

Hyperlipidic Diet ◽

And Oxidative Stress

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Galantamine alleviates oxidative stress alongside anti-inflammatory and cardio-metabolic effects in subjects with the metabolic syndrome in a randomized trial

10.1101/2019.12.30.19016105 ◽

2020 ◽

Author(s):

Carine Teles Sangaleti ◽

Keyla Yukari Katayama ◽

Kátia De Angelis ◽

Tércio Lemos de Moraes ◽

Amanda Aparecida Araújo ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Metabolic Syndrome ◽

Autonomic Regulation ◽

Metabolic Effects ◽

Antioxidant Enzyme Activities ◽

Low Grade ◽

The Metabolic Syndrome ◽

Inflammatory State ◽

Anti Inflammatory

AbstractBackgroundThe metabolic syndrome (MetS) is an obesity-driven disorder with pandemic proportions and limited treatment options. Oxidative stress, low-grade inflammation and altered autonomic regulation, are important components of MetS pathophysiology. We recently reported that galantamine, an acetylcholinesterase inhibitor and an FDA-approved drug (for Alzheimer’s disease) alleviates the inflammatory state in MetS subjects. Here we examined the effects of galantamine on oxidative stress in parallel with inflammatory and cardio-metabolic parameters in subjects with MetS.MethodsThe effects of galantamine treatment, 8 mg daily for 4 weeks, followed by 16 mg daily for 8 weeks or placebo were studied in randomly assigned subjects with MetS (n=22 per group) of both genders. Oxidative stress, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase activities, lipid and protein peroxidation, and nitrite levels were analyzed before and at the end of the treatment. In addition, plasma cytokine and adipokine levels, insulin resistance (HOMA-IR) and other relevant cardio-metabolic indices were analyzed. Autonomic regulation was also examined by heart rate variability (HRV) before treatment, and at every 4 weeks of treatment.ResultsGalantamine treatment significantly increased antioxidant enzyme activities, including SOD (+1.65 USOD/mg protein, [95% CI 0.39 to 2.92], P=0.004) and CAT (+0.93 nmol/mg, [95% CI 0.34 to 1.51], P=0.011), decreased lipid peroxidation (thiobarbituric acid reactive substances, -5.45 pmol/mg, [95% CI -10.97 to 0.067], P=0.053) and systemic nitrite levels (-0.05 nit/mg protein, [95% CI -0.21 to 0.10], P=0.038) compared with placebo. In addition, galantamine significantly alleviated the inflammatory state and insulin resistance, and decreased the low frequency/high frequency ratio of HRV, following 8 and 12 weeks of drug treatment.ConclusionLow-dose galantamine alleviates oxidative stress, alongside beneficial anti-inflammatory, and metabolic effects, and modulates autonomic regulation in subjects with MetS. These findings are of considerable interest for further studies with galantamine to ameliorate MetS pathophysiology.

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CYP2J2 and EETs Protect Against Pulmonary Hypertension with Lung Ischemia-Reperfusion Injury In Vivo and In Vitro

10.21203/rs.3.rs-855996/v1 ◽

2021 ◽

Author(s):

Yun Ding ◽

Pengjie Tu ◽

Yiyong Chen ◽

Yangyun Huang ◽

Xiaojie Pan ◽

...

Keyword(s):

Oxidative Stress ◽

Inflammatory Response ◽

Reperfusion Injury ◽

Lung Tissue ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Tnf Α ◽

Anti Inflammatory

Abstract Background Cytochrome P450 epoxygenase 2J2 (CYP2J2) metabolizes arachidonic acid to epoxyeicosatrienoic acids (EETs), which exert anti-inflammatory, anti-apoptotic, pro-proliferative, and antioxidant effects on the cardiovascular system. However, the role of CYP2J2 and EETs in pulmonary arterial hypertension (PAH) with lung ischemia-reperfusion injury (LIRI) remains unclear. In the present study, we investigated the effects of CYP2J2 overexpression and exogenous EETs on PAH with LIRI in vitro and in vivo.Methods CYP2J2 gene was transfected into rat lung tissue by recombinant adeno-associated virus (rAAV) to increase the levels of EETs in serum and lung tissue. A rat model of PAH with LIRI was constructed by tail vein injection of monocrotaline (50 mg/kg) for 4 weeks, followed by clamping of the left pulmonary hilum for 1 h and reperfusion for 2 h. In addition, we established a cellular model of human pulmonary artery endothelial cells (HPAECs) with TNF-α combined with hypoxic reoxygenation (anoxia for 8 h and reoxygenation for 16 h) to determine the effect and mechanism of exogenous EETs.Results CYP2J2 overexpression significantly reduced the inflammatory response, oxidative stress and apoptosis associated with lung injury in PAH with LIRI. In addition, exogenous EETs suppressed inflammatory response and reduced intracellular reactive oxygen species (ROS) production and inhibited apoptosis in a tumor necrosis factor alpha (TNF-α) combined hypoxia-reoxygenation model of HPAECs. Our further studies revealed that the anti-inflammatory effects of CYP2J2 overexpression and EETs might be mediated by PPARγ pathway; the anti-apoptotic effects might be mediated by the PI3K/Ak pathway.Conclusions CYP2J2 overexpression and EETs protect against PAH with LIRI via anti-inflammation, anti-oxidative stress and anti-apoptosis, suggesting that increased levels of EETs may be a promising strategy for the prevention and treatment of PAH with LIRI.

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Effect of Electroacupuncture on Spinal Cord Injury in Mice: Inhibition Of Inflammatory Response and Oxidative Stress via ApoE and Nrf2

10.21203/rs.3.rs-22504/v1 ◽

2020 ◽

Author(s):

Ni Dai ◽

Chenglin Tang ◽

Hongdi Zhao ◽

Pan Dai ◽

Siqin Huang

Keyword(s):

Oxidative Stress ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Inflammatory Response ◽

Inflammatory Cytokines ◽

Neuroprotective Effect ◽

Related Factor ◽

Cord Injury ◽

Anti Inflammatory ◽

And Oxidative Stress

Abstract Background: Spinal cord injury (SCI) is a catastrophic central nervous system disease. Inflammatory response and oxidative stress are two critical factors in the pathophysiological process of SCI and closely involved with Apolipoprotein E(ApoE) and Nuclear factor erythroid 2-related factor (Nrf2). Electroacupuncture (EA) has perfectly neuroprotective effect on SCI. However, the underlying mechanism by which EA mediates the inflammatory response and oxidative stress is not completely elucidated. In the present study, we investigated the signaling pathways that EA regulates inflammatory response and oxidative stress through elevation of ApoE and Nrf2 after SCI.Methods: C57BL/6 Wide Type (WT) mice and ApoE -/- mice were subjected to SCI model by a serrefine clamping. Neurological function was detected by BMS scores, ultrastructure of demyelinationed axons was observed by transmission electron microscopy. ApoE, pro- and anti- inflammatory cytokines, oxidative stress-relevant proteins were determined by histochemistry technology. Two-way ANOVA was applied to BMS scores. One-way ANOVA and Bonferroni's multiple comparison test were used to analyse differences among groups.Results: BMS scores were increased gradually and demyelinated axons were improved by EA gradually with the expression of ApoE. EA can inhibit inflammatory response by activation of ApoE, which decreased pro-inflammatory cytokines(TNF-α, IL-6, and IL-1β) expression and increased anti-inflammatory cytokines(IL-10 and TGF-β1).Meanwhile, EA can also inhibit oxidative stress by elevation of Nrf2,which induced HO-1 and NQO1 expression in WT and ApoE -/- mice.Conclusions: EA is a reliable treatment for promoting functional recovery of SCI. Thesynergisticrole of ApoE and Nrf2 in EA regulating inflammatory response and oxidative stress is decisiveto recovery after SCI.

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