The diverse biological properties of the chemically inert noble gases

Winkler, David A.; Thornton, Aaron W.; Farjot, Géraldine; Katz, Ira

doi:10.1016/j.pharmthera.2016.02.002

Cited by 52 publications

(61 citation statements)

References 142 publications

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“…Their chemical inertness is due to a filled valence shell that prevents covalent bonds with other molecules under standard temperature and pressure conditions (Spaggiari et al 2013). Despite that, xenon and also other noble gases exhibit interesting biological properties (Deng et al 2014;Winkler et al 2016), probably because of interactions with cell components through noncovalent forces (Liu et al 2010;Sauguet et al 2016).…”

Section: Introductionmentioning

confidence: 99%

“…Xenon is without doubt the noble gas whose biological effects are the most robust and best documented. Xenon can operate as an anesthetic (Jordan and Wright 2010;Winkler et al 2016) and it possesses analgesic properties (Esencan et al 2013). Xenon also exerts rapid antidepressant-like effects (Dandekar et al 2018) and ameliorates l-dopainduced dyskinesia in experimental Parkinsonism (Baufreton et al 2018).…”

Section: Introductionmentioning

confidence: 99%

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Neuroprotection of dopamine neurons by xenon against low-level excitotoxic insults is not reproduced by other noble gases

et al. 2019

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Using midbrain cultures, we previously demonstrated that the noble gas xenon is robustly protective for dopamine (DA) neurons exposed to l-trans-pyrrolidine-2,4-dicarboxylate (PDC), an inhibitor of glutamate uptake used to generate sustained, low-level excitotoxic insults. DA cell rescue was observed in conditions where the control atmosphere for cell culture was substituted with a gas mix, comprising the same amount of oxygen (20%) and carbon dioxide (5%) but 75% of xenon instead of nitrogen. In the present study, we first aimed to determine whether DA cell rescue against PDC remains detectable when concentrations of xenon are progressively reduced in the cell culture atmosphere. Besides, we also sought to compare the effect of xenon to that of other noble gases, including helium, neon and krypton. Our results show that the protective effect of xenon for DA neurons was concentration-dependent with an IC 50 estimated at about 44%. We also established that none of the other noble gases tested in this study protected DA neurons from PDC-mediated insults. Xenon's effectiveness was most probably due to its unique capacity to block NMDA glutamate receptors. Besides, mathematical modeling of gas diffusion in the culture medium revealed that the concentration reached by xenon at the cell layer level is the highest of all noble gases when neurodegeneration is underway. Altogether, our data suggest that xenon may be of potential therapeutic value in Parkinson disease, a chronic neurodegenerative condition where DA neurons appear vulnerable to slow excitotoxicity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neuroprotection of dopamine neurons by xenon against low-level excitotoxic insults is not reproduced by other noble gases

et al. 2019

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“…While lipid solubility (e.g., the Meyer–Overton correlation, polar narcosis) plays a role in the anesthetic properties of noble gases, specific molecular mechanisms underlying the rich spectrum of potentially useful properties remain largely unexplored. The literature on biological and clinical properties of the noble gases was reviewed recently . Unlike small molecule drugs, where extensive biology, pharmacology, pharmacokinetics, and toxicology studies are performed before clinical use, xenon in particular has been used in humans and animals before comprehensive biochemical studies have been conducted.…”

Section: Introductionmentioning

confidence: 99%

“…The few reported computational studies of noble gas interaction with proteins have been reviewed recently by Winkler et al . These studies suggest that relatively simple force fields are sufficient to identify the likely binding sites of noble gases.…”

Section: Introductionmentioning

confidence: 99%

Decoding the Rich Biological Properties of Noble Gases: How Well Can We Predict Noble Gas Binding to Diverse Proteins?

et al. 2018

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The chemically inert noble gases display a surprisingly rich spectrum of useful biological properties. Relatively little is known about the molecular mechanisms behind these effects. It is clearly not feasible to conduct large numbers of pharmacological experiments on noble gases to identify activity. Computational studies of the binding of noble gases and proteins can address this paucity of information and provide insight into mechanisms of action. We used bespoke computational grid calculations to predict the positions of energy minima in the interactions of noble gases with diverse proteins. The method was validated by quantifying how well simulations could predict binding positions in 131 diverse protein X-ray structures containing 399 Xe and Kr atoms. We found excellent agreement between calculated and experimental binding positions of noble gases. 94 % of all crystallographic xenon atoms were within 1 Xe van der Waals (vdW) diameter of a predicted binding site, and 97 % lay within 2 vdW diameters. 100 % of crystallographic krypton atoms were within 1 Kr vdW diameter of a predicted binding site. We showed the feasibility of large-scale computational screening of all ≈60 000 unique structures in the Protein Data Bank. This will elucidate biochemical mechanisms by which these novel 'atomic drugs' elicit their valuable biochemical properties and identify new medical uses.

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“…[9] It can enhance lipopolysaccharide-induced interleukin-1 beta (IL-1β) expression in microglia by activating extracellular signal-regulated kinase 1/2, [10] inhibiting caspase-3 activation and cytochrome c release from cells, [11] and reducing serum levels of the pro-inflammatory cytokines, such as IL-1, IL-6, and tumor necrosis factor alpha (TNFα) in rats. [12,13] In addition, in recent years, it was shown that xenon had neuroprotective, cardioprotective, and renoprotective effects in different animal models subjected to preconditioning, real-time conditioning, and postconditioning.…”

Section: Introductionmentioning

confidence: 99%

Effects of pulmonary static inflation with 50% xenon on oxygen impairment during cardiopulmonary bypass for stanford type A acute aortic dissection

Jin¹,

Yang²,

Pan

et al. 2017

Medicine

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The diverse biological properties of the chemically inert noble gases

Cited by 52 publications

References 142 publications

Neuroprotection of dopamine neurons by xenon against low-level excitotoxic insults is not reproduced by other noble gases

Neuroprotection of dopamine neurons by xenon against low-level excitotoxic insults is not reproduced by other noble gases

Decoding the Rich Biological Properties of Noble Gases: How Well Can We Predict Noble Gas Binding to Diverse Proteins?

Effects of pulmonary static inflation with 50% xenon on oxygen impairment during cardiopulmonary bypass for stanford type A acute aortic dissection

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