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Critical Care (London, England) 2010Certain noble gases, though inert, exhibit remarkable biological properties. Notably, xenon and argon provide neuroprotection in animal models of central nervous system...
Certain noble gases, though inert, exhibit remarkable biological properties. Notably, xenon and argon provide neuroprotection in animal models of central nervous system injury. In the previous issue of Critical Care, Loetscher and colleagues provided further evidence that argon may have therapeutic properties for neuronal toxicity by demonstrating protection against both traumatic and oxygen-glucose deprivation injury of organotypic hippocampal cultures in vitro. Their data are of interest as argon is more abundant, and therefore cheaper, than xenon (the latter of which is currently in clinical trials for perinatal hypoxic-ischemic brain injury; TOBYXe; NCT00934700). We eagerly await in vivo data to complement the promising in vitro data hailing argon neuroprotection.
Topics: Animals; Argon; Central Nervous System; In Vitro Techniques; Models, Animal; Neuroprotective Agents
PubMed: 20236500
DOI: 10.1186/cc8847 -
Journal of Molecular Cell Biology Apr 2023Neuroinflammation plays a vital role in cerebral ischemic stroke (IS). In the acute phase of IS, microglia are activated toward the pro-inflammatory (M1) and...
Neuroinflammation plays a vital role in cerebral ischemic stroke (IS). In the acute phase of IS, microglia are activated toward the pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. Argon, an inert gas, can reduce neuroinflammation and alleviate ischemia/reperfusion (I/R) injury. However, whether argon regulates M1/M2 polarization to protect against I/R injury as well as the underlying mechanism has not been reported. In this study, we analyzed the activation and polarization of microglia after I/R injury with or without argon administration and explored the effects of argon on NLRP3 inflammasome-mediated inflammation in microglia in vitro and in vivo. The results showed that argon application inhibited the activation of M1 microglia/macrophage in the ischemic penumbra and the expression of proteins related to NLRP3 inflammasome and pyroptosis in microglia. Argon administration also inhibited the expression and processing of IL-1β, a primary pro-inflammatory cytokine. Thus, argon alleviates I/R injury by inhibiting pro-inflammatory reactions via suppressing microglial polarization toward M1 phenotype and inhibiting the NF-κB/NLRP3 inflammasome signaling pathway. More importantly, we showed that argon worked better than the specific NLRP3 inflammasome inhibitor MCC950 in suppressing neuroinflammation and protecting against cerebral I/R injury, suggesting the therapeutic potential of argon in neuroinflammation-related neurodegeneration diseases as a potent gas inhibitor of the NLRP3 inflammasome signaling pathway.
Topics: Humans; NF-kappa B; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Argon; Neuroinflammatory Diseases; Signal Transduction; Inflammation; Microglia
PubMed: 36574951
DOI: 10.1093/jmcb/mjac077 -
International Journal of Molecular... Oct 2016The noble gas argon has attracted increasing attention in recent years, especially because of its neuroprotective properties. In a variety of models, ranging from... (Review)
Review
The noble gas argon has attracted increasing attention in recent years, especially because of its neuroprotective properties. In a variety of models, ranging from oxygen-glucose deprivation in cell culture to complex models of mid-cerebral artery occlusion, subarachnoid hemorrhage or retinal ischemia-reperfusion injury in animals, argon administration after individual injury demonstrated favorable effects, particularly increased cell survival and even improved neuronal function. As an inert molecule, argon did not show signs of adverse effects in the in vitro and in vivo model used, while being comparably cheap and easy to apply. However, the molecular mechanism by which argon is able to exert its protective and beneficial characteristics remains unclear. Although there are many pieces missing to complete the signaling pathway throughout the cell, it is the aim of this review to summarize the known parts of the molecular pathways and to combine them to provide a clear insight into the cellular pathway, starting with the receptors that may be involved in mediating argons effects and ending with the translational response.
Topics: Animals; Argon; Disease Models, Animal; Humans; Intracellular Space; Neuroprotection; Neuroprotective Agents; Signal Transduction
PubMed: 27809248
DOI: 10.3390/ijms17111816 -
British Journal of Anaesthesia Aug 2022The noble gases argon and xenon are potential novel neuroprotective treatments for acquired brain injuries. Xenon has already undergone early-stage clinical trials in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The noble gases argon and xenon are potential novel neuroprotective treatments for acquired brain injuries. Xenon has already undergone early-stage clinical trials in the treatment of ischaemic brain injuries, with mixed results. Argon has yet to progress to clinical trials as a treatment for brain injury. Here, we aim to synthesise the results of preclinical studies evaluating argon and xenon as neuroprotective therapies for brain injuries.
METHODS
After a systematic review of the MEDLINE and Embase databases, we carried out a pairwise and stratified meta-analysis. Heterogeneity was examined by subgroup analysis, funnel plot asymmetry, and Egger's regression.
RESULTS
A total of 32 studies were identified, 14 for argon and 18 for xenon, involving measurements from 1384 animals, including murine, rat, and porcine models. Brain injury models included ischaemic brain injury after cardiac arrest (CA), neurological injury after cardiopulmonary bypass (CPB), traumatic brain injury (TBI), and ischaemic stroke. Both argon and xenon had significant (P<0.001), positive neuroprotective effect sizes. The overall effect size for argon (CA, TBI, stroke) was 18.1% (95% confidence interval [CI], 8.1-28.1%), and for xenon (CA, TBI, stroke) was 34.1% (95% CI, 24.7-43.6%). Including the CPB model, only present for xenon, the xenon effect size (CPB, CA, TBI, stroke) was 27.4% (95% CI, 11.5-43.3%). Xenon, both with and without the CPB model, was significantly (P<0.001) more protective than argon.
CONCLUSIONS
These findings provide evidence to support the use of xenon and argon as neuroprotective treatments for acquired brain injuries. Current evidence suggests that xenon is more efficacious than argon overall.
Topics: Animals; Argon; Brain Injuries; Brain Ischemia; Heart Arrest; Mice; Neuroprotection; Neuroprotective Agents; Noble Gases; Rats; Stroke; Swine; Xenon
PubMed: 35688658
DOI: 10.1016/j.bja.2022.04.016 -
International Journal of Molecular... Oct 2014Argon belongs to the group of noble gases, which are regarded as chemically inert. Astonishingly some of these gases exert biological properties and during the last... (Review)
Review
Argon belongs to the group of noble gases, which are regarded as chemically inert. Astonishingly some of these gases exert biological properties and during the last decades more and more reports demonstrated neuroprotective and organoprotective effects. Recent studies predominately use in vivo or in vitro models for ischemic pathologies to investigate the effect of argon treatment. Promising data has been published concerning pathologies like cerebral ischemia, traumatic brain injury and hypoxic ischemic encephalopathy. However, models applied and administration of the therapeutic gas vary. Here we provide a systematic review to summarize the available data on argon's neuro- and organoprotective effects and discuss its possible mechanism of action. We aim to provide a summary to allow further studies with a more homogeneous setting to investigate possible clinical applications of argon.
Topics: Animals; Argon; Brain; Brain Injuries; Brain Ischemia; Humans; Neuroprotective Agents
PubMed: 25310646
DOI: 10.3390/ijms151018175 -
Theranostics 2019Diabetic foot ulcers are associated with significant morbidity and mortality, and current treatments are far from optimal. Chronic wounds in diabetes are characterised...
Diabetic foot ulcers are associated with significant morbidity and mortality, and current treatments are far from optimal. Chronic wounds in diabetes are characterised by impaired angiogenesis, leukocyte function, fibroblast proliferation, and keratinocyte migration and proliferation. : We tested the effect of exposure to argon gas on endothelial cell, fibroblast, macrophage and keratinocyte cell cultures and of a streptozotocin-induced diabetic mouse model. : Exposure to normobaric argon gas promotes multiple steps of the wound healing process. Argon accelerated angiogenesis, associated with upregulation of pro-angiogenic Angiopoietin-1 and vascular endothelial growth factor (VEGF) signalling and . Treatment with argon enhanced expression of transforming growth factor (TGF)-β, early recruitment of macrophages and keratinocyte proliferation. Argon had a pro-survival effect, inducing expression of cytoprotective mediators B-cell lymphoma 2 and heme oxygenase 1. Argon was able to accelerate wound closure in a diabetic mouse model. : Together these findings indicate that argon gas may be a promising candidate for clinical use in treatment of diabetic ulcers.
Topics: Animals; Argon; Cells, Cultured; Diabetes Mellitus; Diabetic Foot; Disease Models, Animal; Endothelial Cells; Fibroblasts; Keratinocytes; Macrophages; Mice; Neovascularization, Physiologic; Treatment Outcome; Wound Healing
PubMed: 30809288
DOI: 10.7150/thno.29361 -
British Journal of Anaesthesia Mar 2018Despite the global burden of brain injury, neuroprotective agents remain elusive. There are no clinically effective therapies which reduce mortality or improve long-term... (Review)
Review
Despite the global burden of brain injury, neuroprotective agents remain elusive. There are no clinically effective therapies which reduce mortality or improve long-term cognitive outcome. Ventilation could be an easily modifiable variable in resuscitation; gases are relatively simple to administer. Xenon is the prototypic agent of a new generation of experimental treatments which show promise. However, use is hindered by its prohibitive cost and anaesthetic properties. Argon is an attractive option, being cheaper, easy to transport, non-sedating, and mechanistically distinct from xenon. In vitro and in vivo models provide evidence of argon reducing brain injury, with improvements in neurocognitive, histological, and biomarker metrics, as well as improved survival. Current data suggest that the effect of argon is mediated via the toll-like receptors 2 and 4, the extracellular signal-regulated kinase 1/2, and phosphatidylinositol 3 kinase (PI-3K)-AKT pathways. Ventilation with argon appears to be safe in pigs and preliminary human trials. Given recent evidence that arterial hyperoxia may be harmful, the supplementation of high-concentration argon may not necessitate changes to clinical practice. Given the logistic benefits, and the evidence for argon neuroprotection summarized in this manuscript, we believe that the time has come to consider developing Phase II clinical trials to assess its benefit in acute neurological injury.
Topics: Animals; Argon; Brain Injuries; Disease Models, Animal; Humans; Neuroprotection; Neuroprotective Agents
PubMed: 29452802
DOI: 10.1016/j.bja.2017.10.017 -
Biomolecules Sep 2022This paper aims to review the evidence of the cellular activity on titanium samples exposed to Plasma of Argon (PoA) treatment. A systematic review was carried out based... (Review)
Review
This paper aims to review the evidence of the cellular activity on titanium samples exposed to Plasma of Argon (PoA) treatment. A systematic review was carried out based on the PRISMA statement by searching the Cochrane Library, PubMed, Web of Science, EMBASE and Scopus, up to October 2020. Papers were selected according to PICOS format that is: Population (P): osteoblasts, fibroblasts, gingival cells; Intervention (I): PoA disinfection treatment; Comparison (C): untreated controls; Outcome (O): cell culture; Setting (S): in vitro assays. The quality assessment was performed according to the CRIS Guidelines (Checklist for Reporting In vitro Studies). A total of 661 articles were found, of which 16 were included. The quality assessment revealed an overall poor quality of the studies analyzed. In vitro studies on the potential of PoA showed a potential effect in promoting higher cell adhesion and protein adsorption in the earliest times (hours). This outcome was not so evident when later stages of cell growth on the surfaces were tested and compared to the control groups. Only one study was conducted in vivo on a human sample regarding abutment cleaning. No meta-analysis was conducted because of the variety of experimental settings, mixed methods and different cell lines studied. PoA seems to be effective in promoting cell adhesion and protein adsorption. The duration of this effect remains unclear. Further evidence is required to demonstrate the long-term efficacy of the treatment and to support the use of PoA treatment in clinical practice.
Topics: Argon; Cell Adhesion; Humans; Osteoblasts; Surface Properties; Titanium
PubMed: 36139059
DOI: 10.3390/biom12091219 -
Medical Gas Research 2023The noble gas argon has demonstrated biological activity that may prove useful as a medical intervention. Pharmacokinetics, the disposition of the drug molecule in the...
The noble gas argon has demonstrated biological activity that may prove useful as a medical intervention. Pharmacokinetics, the disposition of the drug molecule in the body through time, is fundamental necessary knowledge to drug discovery, development and even post-marketing. The fundamental measurement in pharmacokinetic studies is blood concentration of the molecule (and its metabolites) of interest. While a physiologically based model of argon pharmacokinetics has appeared in the literature, no experimental data have been published. Thus, argon pharmaceutical development requires measurement of argon solubility in blood. This paper reports on the development of a technique based on mass spectrometry for measuring argon solubility in liquids, including blood, to be further employed in pharmacokinetics testing of argon. Based on a prototype, results are reported from sensitivity experiments using ambient air, water and rabbit blood. The key takeaway is that the system was sensitive to argon during all of the testing. We believe the technique and prototype of the quadrupole mass spectrometer gas analyzer will be capable of inferring argon pharmacokinetics through the analysis of blood samples.
Topics: Animals; Rabbits; Argon; Solubility; Mass Spectrometry; Air; Water
PubMed: 37077120
DOI: 10.4103/2045-9912.351106 -
International Journal of Molecular... Mar 2021Argon inhalation attenuates multiorgan failure (MOF) after experimental ischemic injury. We hypothesized that this protection could involve decreased High Mobility Group...
Argon inhalation attenuates multiorgan failure (MOF) after experimental ischemic injury. We hypothesized that this protection could involve decreased High Mobility Group Box 1 (HMGB1) systemic release. We investigated this issue in an animal model of MOF induced by aortic cross-clamping. Anesthetized rabbits were submitted to supra-coeliac aortic cross-clamping for 30 min, followed by 300 min of reperfusion. They were randomly divided into three groups ( = 7/group). The Control group inhaled nitrogen (70%) and oxygen (30%). The Argon group was exposed to a mixture of argon (70%) and oxygen (30%). The last group inhaled nitrogen/oxygen (70/30%) with an administration of the HMGB1 inhibitor glycyrrhizin (4 mg/kg i.v.) 5 min before aortic unclamping. At the end of follow-up, cardiac output was significantly higher in Argon and Glycyrrhizin vs. Control (60 ± 4 and 49 ± 4 vs. 33 ± 8 mL/kg/min, respectively). Metabolic acidosis was attenuated in Argon and Glycyrrhizin vs. Control, along with reduced amount of norepinephrine to reverse arterial hypotension. This was associated with reduced interleukin-6 and HMGB1 plasma concentration in Argon and Glycyrrhizin vs. Control. End-organ damages were also attenuated in the liver and kidney in Argon and Glycyrrhizin vs. Control, respectively. Argon inhalation reduced HMGB1 blood level after experimental aortic cross-clamping and provided similar benefits to direct HMGB1 inhibition.
Topics: Animals; Argon; Biopsy; Blood Pressure; Cardiac Output; Cytokines; Disease Models, Animal; HMGB1 Protein; Heart Function Tests; Hemodynamics; Immunohistochemistry; Male; Multiple Organ Failure; Rabbits
PubMed: 33806919
DOI: 10.3390/ijms22063257