Methane and Inflammation - A Review (Fight Fire with Fire)

AbstractMammalian methanogenesis is regarded as an indicator of carbohydrate fermentation by anaerobic gastrointestinal flora. Once generated by microbes or released by a non-bacterial process, methane is generally considered to be biologically inactive. However, recent studies have provided evidence for methane bioactivity in various in vivo settings. The administration of methane either in gas form or solutions has been shown to have anti-inflammatory and neuroprotective effects in an array of experimental conditions, such as ischemia/reperfusion, endotoxemia and sepsis. It has also been demonstrated that exogenous methane influences the key regulatory mechanisms and cellular signalling pathways involved in oxidative and nitrosative stress responses. This review offers an insight into the latest findings on the multi-faceted organ protective activity of exogenous methane treatments with special emphasis on its versatile effects demonstrated in sepsis models.

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Bioactivity of Inhaled Methane and Interactions With Other Biological Gases

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.824749 ◽

2022 ◽

Vol 9 ◽

Author(s):

László Juhász ◽

Szabolcs Péter Tallósy ◽

Anna Nászai ◽

Gabriella Varga ◽

Dániel Érces ◽

...

Keyword(s):

Stress Responses ◽

Mitochondrial Respiration ◽

Nitrosative Stress ◽

Oxidative And Nitrosative Stress ◽

Key Events

A number of studies have demonstrated explicit bioactivity for exogenous methane (CH4), even though it is conventionally considered as physiologically inert. Other reports cited in this review have demonstrated that inhaled, normoxic air-CH4 mixtures can modulate the in vivo pathways involved in oxidative and nitrosative stress responses and key events of mitochondrial respiration and apoptosis. The overview is divided into two parts, the first being devoted to a brief review of the effects of biologically important gases in the context of hypoxia, while the second part deals with CH4 bioactivity. Finally, the consequence of exogenous, normoxic CH4 administration is discussed under experimental hypoxia- or ischaemia-linked conditions and in interactions between CH4 and other biological gases, with a special emphasis on its versatile effects demonstrated in pulmonary pathologies.

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A Possible Novel Anti-Inflammatory Mechanism for the Pharmacological Prolyl Hydroxylase Inhibitor 3,4-Dihydroxybenzoate: Implications for Use as a Therapeutic for Parkinson’s Disease

Parkinson s Disease ◽

10.1155/2012/364684 ◽

2012 ◽

Vol 2012 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Shankar J. Chinta ◽

Subramanian Rajagopalan ◽

Abirami Ganesan ◽

Julie K. Andersen

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Microglial Activation ◽

Nitrosative Stress ◽

Neurodegenerative Disorder ◽

Oxidative And Nitrosative Stress ◽

Prolyl Hydroxylases ◽

Age Related

Parkinson’s disease (PD) is an age-related neurodegenerative disorder characterized in part by the preferential loss of nigrostriatal dopaminergic neurons. Although the precise etiology of PD is unknown, accumulating evidence suggests that PD involves microglial activation that exerts neurotoxic effects through production of proinflammatory cytokines and increased oxidative and nitrosative stress. Thus, controlling microglial activation has been suggested as a therapeutic target for combating PD. Previously we demonstrated that pharmacological inhibition of a class of enzymes known as prolyl hydroxylases via 3,4-dihydroxybenzoate administration protected against MPTP-induced neurotoxicity, however the exact mechanisms involved were not elucidated. Here we show that this may be due to DHB’s ability to inhibit microglial activation. DHB significantly attenuated LPS-mediated induction of nitric oxide synthase and pro-inflammatory cytokines in murine BV2 microglial cellsin vitroin conjunction with reduced ROS production and activation of NFκB and MAPK pathways possibly due to up-regulation of HO-1 levels. HO-1 inhibition partially abrogates LPS-mediated NFκB activity and subsequent NO induction.In vivo, DHB pre-treatment suppresses microglial activation elicited by MPTP treatment. Our results suggest that DHB’s neuroprotective properties could be due to its ability to dampen induction of microglial activation via induction of HO-1.

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Octreotide and lanreotide decrease ovarian ischemia–reperfusion injury in rats by improving oxidative and nitrosative stress

Journal of Obstetrics and Gynaecology Research ◽

10.1111/jog.14379 ◽

2020 ◽

Vol 46 (10) ◽

pp. 2050-2058

Author(s):

Senol Kalyoncu ◽

Bulent Yilmaz ◽

Mustafa Demir ◽

Meltem Tuncer ◽

Zehra Bozdag ◽

...

Keyword(s):

Reperfusion Injury ◽

Nitrosative Stress ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Oxidative And Nitrosative Stress

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ROS-Dependent Neuroprotective Effects of NaHS in Ischemia Brain Injury Involves the PARP/AIF Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000430317 ◽

2015 ◽

Vol 36 (4) ◽

pp. 1539-1551 ◽

Cited By ~ 35

Author(s):

Qian Yu ◽

Zhihong Lu ◽

Lei Tao ◽

Lu Yang ◽

Yu Guo ◽

...

Keyword(s):

Brain Injury ◽

Focal Cerebral Ischemia ◽

Ischemia Reperfusion ◽

Dependent Manner ◽

Neuroprotective Effects ◽

Ht22 Cells ◽

In Vivo Models ◽

The Brain

Background/Aims: Stroke is among the top causes of death worldwide. Neuroprotective agents are thus considered as potentially powerful treatment of stroke. Methods: Using both HT22 cells and male Sprague-Dawley rats as in vitro and in vivo models, we investigated the effect of NaHS, an exogenous donor of H2S, on the focal cerebral ischemia-reperfusion (I/R) induced brain injury. Results: Administration of NaHS significantly decreased the brain infarcted area as compared to the I/R group in a dose-dependent manner. Mechanistic studies demonstrated that NaHS-treated rats displayed significant reduction of malondialdehyde content, and strikingly increased activity of superoxide dismutases and glutathione peroxidase in the brain tissues compared with I/R group. The enhanced antioxidant capacity as well as restored mitochondrial function are NaHS-treatment correlated with decreased cellular reactive oxygen species level and compromised apoptosis in vitro or in vivo in the presence of NaHS compared with control. Further analysis revealed that the inhibition of PARP-1 cleavage and AIF translocation are involved in the neuroprotective effects of NaHS. Conclusion: Collectively, our results suggest that NaHS has potent protective effects against the brain injury induced by I/R. NaHS is possibly effective through inhibition of oxidative stress and apoptosis.

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Effect of modulation of hydrogen sulfur and glutathione synthesis on oxidative and nitrosative metabolism under myocardial ischemia-reperfusion

Bulletin of Taras Shevchenko National University of Kyiv Series Biology ◽

10.17721/1728_2748.2021.84.43-47 ◽

2021 ◽

Vol 84 (1) ◽

pp. 43-47

Author(s):

R. Fedichkina ◽

Yu. Korkach ◽

I. Okhai ◽

Yu. Goshovska ◽

V. Sagach

Keyword(s):

Nitrosative Stress ◽

Heart Function ◽

Ischemia Reperfusion ◽

Redox Balance ◽

Isolated Rat Heart ◽

Cardioprotective Effect ◽

Ros Generation ◽

Synthesis Inhibitor ◽

Oxidative And Nitrosative Stress ◽

Cardiac Tissues

Redox balance maintaining is a prerequisite for normal cardiomyocytes metabolism. Reperfusion injury of the heart is characterized by an explosive increase in ROS generation, cell membranes damage, dysfunction of proteins, the development of muscle contracture etc. It was shown that the hydrogen sulfide (H2S) and the precursor of its synthesis the amino acid L-cysteine provided cardioprotective effect against ischemiareperfusion, In addition, L-cysteine is one of amino acids that form an antioxidant glutathione (GSH). The aim of our work was to investigate the effect of GSH and H2S synthesis modulation on the oxidative and nitrosative stress in cardiac tissues under conditions of ischemia-reperfusion. The H2S synthesis inhibitor propargylglycine (PAG), the GSH synthesis inhibitor butionine sulfoxime (BSO) and L-cysteine were administered intraperitoneally. Next, ischemia-reperfusion of the Langendorff isolated rat heart was performed. In the tissues of rat's hearts, before and after ischemia, we determined the rate of ROS generation, content of POL products, the activity of NO synthesizing enzymes. Results of our study showed that pretreatment with PAG + L-cysteine combination prevented heart function disturbances, ROS formation, increased low molecular weight nitrosothiols content, preserved the activity of constitutive NOS and inhibited the activity of inducible NOS in the pre-ischemic period as well as in the period of reperfusion. Pretreatment with BSO in PAG + L-cysteine group significantly reduced the effectiveness of the combination and abolished cardioprotective effect. Generation of superoxide and hydroxyl anions was increased, activity of inducible NO-synthase was 3.5-fold increased comparing with PAG + L-cysteine pretreated group. Pretreatment with PAG + L-cysteine combination inhibited the formation of ROS and preserved the activity of constitutive NOS, thus providing stable production of NO. Pretreatment with BSO completely abolished an antioxidant effect of PAG + L-cysteine decreasing bioavailability of glutathione.

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OM-MSCs Alleviate the Golgi Apparatus Stress Response following Cerebral Ischemia/Reperfusion Injury via the PEDF-PI3K/Akt/mTOR Signaling Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/4805040 ◽

2021 ◽

Vol 2021 ◽

pp. 1-19

Author(s):

Jialin He ◽

Jianyang Liu ◽

Yan Huang ◽

Xiangqi Tang ◽

Han Xiao ◽

...

Keyword(s):

Ischemic Stroke ◽

Stress Response ◽

Cerebral Ischemia ◽

Stress Responses ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Cerebral Ischemia Reperfusion ◽

Cerebral Ischemia Reperfusion Injury

The mechanism of Golgi apparatus (GA) stress responses mediated by GOLPH3 has been widely studied in ischemic stroke, and the neuroprotection effect of olfactory mucosa mesenchymal stem cells (OM-MSCs) against cerebral ischemia/reperfusion injury (IRI) has been preliminarily presented. However, the exact role of OM-MSCs in the GA stress response following cerebral IRI remains to be elucidated. In the present study, we used an oxygen-glucose deprivation/reoxygenation (OGD/R) model and reversible middle cerebral artery occlusion (MCAO) model to simulate cerebral IRI in vitro and in vivo. Our results showed that the level of GOLPH3 protein, reactive oxygen species (ROS), and Ca2+ was upregulated, SPCA1 level was downregulated, and GA fragmentation was increased in ischemic stroke models, and OM-MSC treatment clearly ameliorated these GA stress responses in vitro and in vivo. Subsequently, the knockdown of PEDF in OM-MSCs using PEDF-specific siRNA further demonstrated that secretion of PEDF in OM-MSCs protected OGD/R-treated N2a cells and MCAO rats from GA stress response. Additionally, rescue experiment using specific pathway inhibitors suggested that OM-MSCs could promote the phosphorylation of the PI3K/Akt/mTOR pathway, thereby mitigating OGD/R-induced GA stress response and excessive autophagy. In conclusion, OM-MSCs minimized the GA stress response following cerebral IRI, at least partially, through the PEDF-PI3K/Akt/mTOR pathway.

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Improvement of Cerebral Ischemia-Reperfusion Injury via Regulation of Apoptosis by Exosomes Derived from BDNF-Overexpressing HEK293

BioMed Research International ◽

10.1155/2021/6613510 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Lizong Wang ◽

Jinghan Jiang ◽

Taofeng Zhou ◽

Xiang Xue ◽

Yongjun Cao

Keyword(s):

Cerebral Ischemia ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Hek293 Cells ◽

Neuroprotective Effects ◽

In Vivo Experiments ◽

Cerebral Ischemia Reperfusion ◽

Cerebral Ischemia Reperfusion Injury ◽

Induced Apoptosis

Brain-derived neurotrophic factor (BDNF) provides neuroprotective effects towards therapeutic cerebral ischemia-reperfusion (I/R) injury. This view has been proposed by more and more evidence. However, due to the lack of permeability of the blood-brain barrier (BBB) as well as the brief half-life in serum, clinical application is not widespread. To study the participation of exosomes containing BDNF in I/R, we isolated exosomes from BDNF-overexpressing HEK293. The protective outcomes of exosomes in hypoxia/reoxygenation (H/R) experiments were determined by the use of SY-5Y cells. Exosome-BDNF therapy restrained H/R-induced apoptosis by inhibition of the reducing levels of oxidative stress and calcium ions in the cells while maintaining stable levels of mitochondrial membrane potential in brain cells damaged by I/R. We then constructed a cerebral I/R injury model using SD rats to find the function of BDNF in exosome-mediated neuroprotection. The in vivo experiments conducted established that exosomes from BDNF-overexpressing HEK293 cells improved cerebral I/R injury by concealing neuronal apoptosis. Findings gained demonstrated that BDNF is a part of preventing cerebral I/R injury due to exosome mediation by regulating the cellular internal environment and inhibiting apoptosis.

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Ginkgo biloba and Its Constituent 6-hydroxykynurenic-acid as well as Its Proanthocyanidins Exert Neurorestorative Effects against Cerebral Ischemia

Planta Medica ◽

10.1055/a-1146-2861 ◽

2020 ◽

Vol 86 (10) ◽

pp. 696-707

Author(s):

Jianbiao Yao ◽

Hongxiang Qiao ◽

Zhuming Jin ◽

Ruwei Wang ◽

Haibo Huang ◽

...

Keyword(s):

Cerebral Ischemia ◽

Ginkgo Biloba ◽

Ischemia Reperfusion ◽

Grape Seed ◽

Negative Control ◽

Major Contributor ◽

Sprague Dawley ◽

Neuroprotective Effects ◽

Phenolic Constituents

AbstractNeuroprotective effects against cerebral ischemia/reperfusion (I/R) injury by Ginkgo biloba leaves are commonly attributed to the antioxidant activity of its proanthocyanidins. Furthermore, preliminary experiments identified 6-hydroxykynurenic acid (6-HKA) as a major contributor to this effect of extract of G. biloba leaves (EGb) prepared according to the Chinese Pharmacopoeia (ChP). In order to elucidate the specific contribution of both proanthocyanidins and 6-HKA to the overall neurorestorative effects of this extract according to ChP, EGb ChP was separated into pure 6-HKA and a newly developed Ginkgo proanthocyanidin extract (GPE), enriched in proanthocyanidins but not containing 6-HKA. Male Sprague-Dawley rats were divided into the groups: sham: 8; model (placebo): 25; GPE 80 mg/kg: 13; GPE 40 mg/kg: 13; GPE 20 mg/kg: 16; grape seed extract (negative control) 40 mg/kg: 18; nimodipine (positive control) 2 mg/kg: 8. All non-sham animals were subjected to cerebral I/R injury by occluding the middle cerebral artery with a nylon suture that was removed after 2 h of ischemia to establish reperfusion. For comparison, a parallel series of experiments were performed with 6-HKA. In these in vivo experiments, neurological dysfunctions were reduced by both GPE and 6-HKA, and both average infarct size and concentrations of malondialdehyde (MDA) and super oxide dismutase (SOD) were significantly ameliorated as compared to the model group. This data, therefore, demonstrates that the neuroprotective effects of EGb cannot be explained by a purely chemical antioxidative effect alone as has been previously proposed, especially with regards to the proanthocyanidins. A pharmacological neurorestorative effect of EGb on neurons and brain tissue itself seems to be a much more straightforward explanation for the presented observations. This effect is most likely explained by the synergistic action of both its numerous phenolic constituents (GPE) and 6-hydroxykynurenic acid (6-HKA), which could be identified as one major contributor to the observed activity.

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Neuroprotective Effects of Ginsenosides against Cerebral Ischemia

Molecules ◽

10.3390/molecules24061102 ◽

2019 ◽

Vol 24 (6) ◽

pp. 1102 ◽

Cited By ~ 15

Author(s):

Zhekang Cheng ◽

Meng Zhang ◽

Chengli Ling ◽

Ying Zhu ◽

Hongwei Ren ◽

...

Keyword(s):

Cerebral Ischemia ◽

Ischemia Reperfusion ◽

Ischemic Injury ◽

Neurological Dysfunction ◽

Control Group ◽

Protective Effects ◽

Ginsenoside Rb1 ◽

Neuroprotective Effects

Ginseng has been used worldwide as traditional medicine for thousands of years, and ginsenosides have been proved to be the main active components for their various pharmacological activities. Based on their structures, ginsenosides can be divided into ginseng diol-type A and ginseng triol-type B with different pharmacological effects. In this study, six ginsenosides, namely ginsenoside Rb1, Rh2, Rg3, Rg5 as diol-type ginseng saponins, and Rg1 and Re as triol-type ginseng saponins, which were reported to be effective for ischemia-reperfusion (I/R) treatment, were chosen to compare their protective effects on cerebral I/R injury, and their mechanisms were studied by in vitro and in vivo experiments. It was found that all ginsenosides could reduce reactive oxygen species (ROS), inhibit apoptosis and increase mitochondrial membrane potential in cobalt chloride-induced (CoCl2-induced) PC12 cells injury model, and they could reduce cerebral infarction volume, brain neurological dysfunction of I/R rats in vivo. The results of immunohistochemistry and western blot showed that the expression of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), silencing information regulator (SIRT1) and nuclear transcription factor P65 (NF-κB) in hippocampal CA1 region of some ginsenoside groups were also reduced. In general, the effect on cerebral ischemia of Rb1 and Rg3 was significantly improved compared with the control group, and was the strongest among all the ginsenosides. The effect on SIRT1 activation of ginsenoside Rb1 and the inhibition effect of TLR4/MyD88 protein expression of ginsenoside Rb1 and Rg3 were significantly stronger than that of other groups. The results indicated that ginsenoside Rg1, Rb1, Rh2, Rg3, Rg5 and Re were effective in protecting the brain against ischemic injury, and ginsenoside Rb1 and Rg3 have the strongest therapeutic activities in all the tested ginsenosides. Their neuroprotective mechanism is associated with TLR4/MyD88 and SIRT1 activation signaling pathways, and they can reduce cerebral ischemic injury by inhibiting NF-κB transcriptional activity and the expression of proinflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6).

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