Bioactivity of Inhaled Methane and Interactions With Other Biological Gases

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.

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

Intensive Care Medicine Experimental ◽

10.1186/s40635-019-0278-6 ◽

2019 ◽

Vol 7 (1) ◽

Cited By ~ 4

Author(s):

Marietta Zita Poles ◽

László Juhász ◽

Mihály Boros

Keyword(s):

Stress Responses ◽

Nitrosative Stress ◽

Ischemia Reperfusion ◽

Signalling Pathways ◽

Experimental Conditions ◽

Neuroprotective Effects ◽

Carbohydrate Fermentation ◽

Insight Into

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.

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 ◽

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.

Oxidative and nitrosative stress responses during macrophage–Candida albicansbiofilm interaction

Medical Mycology ◽

10.1093/mmy/myx143 ◽

2017 ◽

Vol 57 (1) ◽

pp. 101-113 ◽

Cited By ~ 2

Author(s):

Julio E Arce Miranda ◽

José L Baronetti ◽

Claudia E Sotomayor ◽

M Gabriela Paraje

Keyword(s):

Stress Responses ◽

Nitrosative Stress ◽

Nano-Boehmite Induced Oxidative and Nitrosative Stress Responses in Vigna radiata L.

Journal of Plant Growth Regulation ◽

10.1007/s00344-021-10303-8 ◽

2021 ◽

Author(s):

Tushar Khare ◽

Dhanashree Dange ◽

Ashwini Jadhav ◽

Varsha Shriram ◽

Suresh Gosavi ◽

...

Keyword(s):

Stress Responses ◽

Vigna Radiata ◽

Nitrosative Stress ◽

Distinct Stress Responses of Two Functional Laccases in Cryptococcus neoformans Are Revealed in the Absence of the Thiol-Specific Antioxidant Tsa1

Eukaryotic Cell ◽

10.1128/ec.4.1.202-208.2005 ◽

2005 ◽

Vol 4 (1) ◽

pp. 202-208 ◽

Cited By ~ 87

Author(s):

Tricia A. Missall ◽

Jason M. Moran ◽

John A. Corbett ◽

Jennifer K. Lodge

Keyword(s):

Nitric Oxide ◽

Cryptococcus Neoformans ◽

Stress Responses ◽

Fungal Pathogens ◽

Nitrosative Stress ◽

Fluorescent Protein ◽

Resistance Mechanisms ◽

Radical Scavenger ◽

Homologous Gene ◽

ABSTRACT Laccases are thought to be important to the virulence of many fungal pathogens by producing melanin, a presumed oxygen radical scavenger. A laccase in Cryptococcus neoformans has been shown to synthesize melanin and contributes to the virulence and the survival in macrophages of this fungal pathogen. One C. neoformans laccase gene, LAC1, previously called CNLAC1, has been extensively studied, and we describe a homologous gene, LAC2, that is found 8 kb away from LAC1 in the genome. In this study we report a role for both laccases, in addition to the thiol peroxidase, Tsa1, in oxidative and nitrosative stress resistance mechanisms of C. neoformans. With use of real-time PCR, similar changes in expression of the two laccase genes occur in response to oxidative and nitrosative stresses, but only the regulation of the LAC2 gene during stress is influenced by Tsa1. Both laccases contribute to melanin production using L-dopa as a substrate and are differentially localized in the cell based on green fluorescent protein fusions. A single deletion of either LAC1 or LAC2 alone had no effect on sensitivity to H2O2 or nitric oxide. However, deletion of either LAC1 or LAC2 in combination with a TSA1 deletion resulted in a slight peroxide sensitivity, and a lac2Δ tsa1Δ deletion strain was sensitive to nitric oxide stress. In addition, the deletion of both laccases reduces survival of C. neoformans in primary macrophages. Based on our expression and functional analysis, we propose a novel model for the interaction of these two systems, which are both important for virulence.

Peroxynitrite is essential for the initiation of cytomegalovirus replication in vitro and in vivo

Access Microbiology ◽

10.1099/acmi.ac2020.po0473 ◽

2020 ◽

Vol 2 (7A) ◽

Author(s):

Pragati Sabberwal ◽

Lucy Chapman ◽

Mathew Clement ◽

Ceri Fielding ◽

David Thomas ◽

...

Keyword(s):

Virus Replication ◽

Stress Responses ◽

Nitrosative Stress ◽

Hcmv Infection ◽

Antiviral Drug ◽

Congenital Infection ◽

Cmv Infection ◽

Novel Approach

Human cytomegalovirus (HCMV) is a pathogenic beta-herpesvirus that establishes a lifelong infection in hosts. It causes significant morbidity and mortality in the immunocompromised and is associated with a range of birth defects following congenital infection. Current therapeutic approaches that target key viral proteins are toxic and antiviral drug resistance is common. Thus, targeting host genes and cellular pathways essential for HCMV infection offers an alternative strategy for the development of antivirals. Here we show that host oxidative/nitrosative stress responses to CMV are critical for virus replication. Oxidative/nitrosative stress occurs due to accumulation of reactive oxygen/nitrogen species (ROS/RNS). Using a range of ROS/RNS scavengers, we identified that peroxynitrite, a powerful oxidant and nitrating agent, dramatically promoted virus replication in both in vitro and in vivo models of CMV infection. HCMV rapidly induced production of intracellular peroxynitrite upon infection. Inhibition of peroxynitrite within the first 24 hours alleviates efficient HCMV infection in both cell-free and cell-associated infection systems, indicating that peroxynitrite may influence pathways necessary for HCMV entry and/or replication. Furthermore, peroxynitrite inhibition also inhibited HCMV reactivation from latency. Interestingly, the neurotransmitter and naturally-occurring peroxynitrite antagonist 5-hydroxytryptamine, commonly known as serotonin, also impinged on HCMV-induced peroxynitrite production and exhibited anti-HCMV activity. Thus, overall, our study demonstrates a novel role for intracellular peroxynitrite in CMV pathogenesis and implies that peroxynitrite could be targeted as a novel approach to inhibiting CMV infection.

S-allylmercaptocysteine scavenges hydroxyl radical and singlet oxygen in vitro and attenuates gentamicin-induced oxidative and nitrosative stress and renal damage in vivo

BMC Clinical Pharmacology ◽

10.1186/1472-6904-4-5 ◽

2004 ◽

Vol 4 (1) ◽

Cited By ~ 74

Author(s):

José Pedraza-Chaverrí ◽

Diana Barrera ◽

Perla D Maldonado ◽

Yolanda I Chirino ◽

Norma A Macías-Ruvalcaba ◽

...

Keyword(s):

Hydroxyl Radical ◽

Singlet Oxygen ◽

Renal Damage ◽

Nitrosative Stress ◽

Multiorgan Development of Oxidative and Nitrosative Stress in LPS-Induced Endotoxemia in C57Bl/6 Mice: DHE-BasedIn VivoApproach

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/7838406 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 7

Author(s):

Bartosz Proniewski ◽

Agnieszka Kij ◽

Barbara Sitek ◽

Eric E. Kelley ◽

Stefan Chlopicki

Keyword(s):

Nitrosative Stress ◽

Oxidant Stress ◽

Elevated Serum ◽

Oxidation Products ◽

Prostaglandin E ◽

No Production ◽

Systemic Delivery ◽

Amyloid A

Detection of free radicals in tissues is challenging. Most approaches rely on incubating excised sections or homogenates with reagents, typically at supraphysiologic oxygen tensions, to finally detect surrogate, nonspecific end products. In the present work, we explored the potential of using intravenously (i.v.) injected dihydroethidine (DHE) to detect superoxide radical (O2∙-) abundancein vivoby quantification of the superoxide-specific DHE oxidation product, 2-hydroxyethidium (2-OH-E+), as well as ethidium (E+) and DHE in multiple tissues in a murine model of endotoxemia induced by lipopolysaccharide (LPS). LPS was injected intraperitoneally (i.p.), while DHE was delivered via the tail vein one hour before sacrifice. Tissues (kidney, lung, liver, and brain) were harvested and subjected to HPLC/fluorescent analysis of DHE and its monomeric oxidation products. In parallel, electron spin resonance (EPR) spin trapping was used to measure nitric oxide (∙NO) production in the aorta, lung, and liver isolated from the same mice. Endotoxemic inflammation was validated by analysis of plasma biomarkers. The concentration of 2-OH-E+varied in the liver, lung, and kidney; however, the ratios of 2-OH-E+/E+and 2-OH-E+/DHE were increased in the liver and kidney but not in the lung or the brain. An LPS-induced robust level of∙NO burst was observed in the liver, whereas the lung demonstrated a moderate yet progressive increase in the rate of∙NO production. Interestingly, endothelial dysfunction was observed in the aorta, as evidenced by decreased∙NO production 6 hours post-LPS injection that coincided with the inflammatory burden of endotoxemia (e.g. elevated serum amyloid A and prostaglandin E2). Combined, these data demonstrate that systemic delivery of DHE affords the capacity to specifically detect O2∙-productionin vivo. Furthermore, the ratio of 2-OH-E+/E+oxidation products in tissues provides a tool for comparative insight into the oxidative environments in various organs. Based on our findings, we demonstrate that the endotoxemic liver is susceptible to both O2∙--mediated and nonspecific oxidant stress as well as nitrosative stress. Oxidant stress in the lung was detected to a lesser extent, thus underscoring a differential response of liver and lung to endotoxemic injury induced by intraperitoneal LPS injection.

Attenuation of Oxidative Stress in HEK 293 Cells by the TCM Constituents Schisanhenol, Baicalein, Resveratrol or Crocetin and Two Defined Mixtures

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j3mw3n ◽

2015 ◽

Vol 18 (4) ◽

pp. 661 ◽

Cited By ~ 3

Author(s):

John Richard Bend ◽

Xue Yan (Iris) Xue Yan Xia ◽

Daofeng Chen ◽

Abudi Awaysheh ◽

Andrea Lo ◽

...

Keyword(s):

Real Time ◽

Molecular Mechanisms ◽

Nitrosative Stress ◽

Fluorescent Protein ◽

Antioxidant Properties ◽

Hek 293 ◽

Hek 293 Cells ◽

293 Cells

PURPOSE: Our working hypothesis is that single bioactive phytochemicals with antioxidant properties that are important constituents of Traditional Chinese Medicine (TCM) and their defined mixtures have potential as chemoprotective agents for chronic conditions characterized by oxidative and nitrosative stress, including Alzheimer’s. Here we evaluate the ability of baicalein, crocetin, trans-resveratrol or schisanhenol and two defined mixtures of these TCM phytochemicals to attenuate the toxicity resulting from exposure to cell permeant t-butyl hydroperoxide (tBPH) in wild-type and bioengineered (to express choline acetyltransferase) HEK 293 cells. METHODS: Endpoints of tBHP-initiated oxidative and nitrosative stress in both types of HEK 293 cells and its attenuation by TCM constituents and mixtures included cytotoxicity (LDH release); depletion of intracellular glutathione (GSH); formation of S-glutathionylated proteins; oxidative changes to the disulfide proteome; and real-time changes in intracellular redox status. RESULTS: At low µM concentrations, each of the TCM constituents and mixtures effectively attenuated intracellular toxicity due to exposure of HEK 293 cells to 50 or 250 µM tBHP for 30 min to 3 h. Confocal microscopy of HEK 293 cells transfected with mutated green fluorescent protein (roGFP2) showed effective attenuation of tBHP oxidation by baicalein in real time. Three redox-regulated proteins prominent in the disulfide proteome of HEK 293 cells were identified by MALDI-TOF mass spectrometry. CONCLUSIONS: We conclude that single TCM chemicals and their simple mixtures have potential for use in adjunct chemoprotective therapy. Advantages of mixtures compared to single TCM constituents include the ability to combine compounds with varying molecular mechanisms of cytoprotection for enhanced biological activity; and to combine chemicals with complementary pharmacokinetic properties to increase half-life and prolong activity in vivo. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Mechanisms of Herbal Nephroprotection in diabetes mellitus

Journal of Diabetes Research ◽

10.1155/2020/5710513 ◽

2020 ◽

Vol 2020 ◽

pp. 1-31

Author(s):

Dorin Dragoș ◽

Maria Mirabela Manea ◽

Delia Timofte ◽

Dorin Ionescu

Keyword(s):

Nitrosative Stress ◽

Protective Action ◽

Protective Mechanisms ◽

Promising Alternative ◽

Drug Classes ◽

Mediators Of Inflammation ◽

The Many

Diabetic nephropathy (DN) is a leading cause of kidney morbidity. Despite the multilayered complexity of the mechanisms involved in the pathogenesis of DN, the conventional treatment is limited to just a few drug classes fraught with the risk of adverse events, including the progression of renal dysfunction. Phytoceuticals offer a promising alternative as they act on the many-sidedness of DN pathophysiology, multitargeting its intricacies. This paper offers a review of the mechanisms underlying the protective action of these phytoagents, including boosting the antioxidant capabilities, suppression of inflammation, averting the proliferative and sclerosing/fibrosing events. The pathogenesis of DN is viewed as a continuum going from the original offense, high glucose, through the noxious products it generates (advanced glycation end-products, products of oxidative and nitrosative stress) and the signaling chains consequently brought into action, to the harmful mediators of inflammation, sclerosis, and proliferation that eventually lead to DN, despite the countervailing attempts of the protective mechanisms. Special attention was given to the various pathways involved, pointing out the ability of the phytoagents to hinder the deleterious ones (especially those leading to, driven by, or associated with TGF-β activation, SREBP, Smad, MAPK, PKC, NF-κB, NLRP3 inflammasome, and caspase), to promote the protective ones (PPAR-α, PPAR-γ, EP4/Gs/AC/cAMP, Nrf2, AMPK, and SIRT1), and to favorably modulate those with potentially dual effect (PI3K/Akt). Many phytomedicines have emerged as potentially useful out of in vitro and in vivo studies, but the scarcity of human trials seriously undermines their usage in the current clinical practice—an issue that stringently needs to be addressed.