Argon: Systematic Review on Neuro- and Organoprotective Properties of an “Inert” Gas

Höllig, Anke; Schug, Anita; Fahlenkamp, Astrid; Rossaint, Rolf; Coburn, Mark

doi:10.3390/ijms151018175

Cited by 50 publications

(51 citation statements)

References 39 publications

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“…Argon, another noble gas, possesses similar protective properties 20 . However, the neuro-protective potential of argon combined with hypothermia has not been explored to date.…”

Section: Discussionmentioning

confidence: 99%

Heme Oxygenase-1 Mediates Neuroprotection Conferred by Argon in Combination with Hypothermia in Neonatal Hypoxia–Ischemia Brain Injury

et al. 2016

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Background Hypoxic–ischemic encephalopathy is a major cause of mortality and disability in the newborn. The authors investigated the protective effects of argon combined with hypothermia on neonatal rat hypoxic–ischemic brain injury. Methods In in vitro studies, rat cortical neuronal cell cultures were challenged by oxygen and glucose deprivation for 90 min and exposed to 70% Ar or N2 with 5% CO2 balanced with O2, at 33°C for 2 h. Neuronal phospho-Akt, heme oxygenase-1 and phospho-glycogen synthase kinase-3β expression, and cell death were assessed. In in vivo studies, neonatal rats were subjected to unilateral common carotid artery ligation followed by hypoxia (8% O2 balanced with N2 and CO2) for 90 min. They were exposed to 70% Ar or N2 balanced with oxygen at 33°, 35°, and 37°C for 2 h. Brain injury was assessed at 24 h or 4 weeks after treatment. Results In in vitro studies, argon–hypothermia treatment increased phospho-Akt and heme oxygenase-1 expression and significantly reduced the phospho-glycogen synthase kinase-3β Tyr-216 expression, cytochrome C release, and cell death in oxygen–glucose deprivation–exposed cortical neurons. In in vivo studies, argon–hypothermia treatment decreased hypoxia/ischemia-induced brain infarct size (n = 10) and both caspase-3 and nuclear factor-κB activation in the cortex and hippocampus. It also reduced hippocampal astrocyte activation and proliferation. Inhibition of phosphoinositide-3-kinase (PI3K)/Akt pathway through LY294002 attenuated cerebral protection conferred by argon–hypothermia treatment (n = 8). Conclusion Argon combined with hypothermia provides neuroprotection against cerebral hypoxia–ischemia damage in neonatal rats, which could serve as a new therapeutic strategy against hypoxic–ischemic encephalopathy.

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“…Argon, another noble gas, possesses similar protective properties 20 . However, the neuro-protective potential of argon combined with hypothermia has not been explored to date.…”

Section: Discussionmentioning

confidence: 99%

Heme Oxygenase-1 Mediates Neuroprotection Conferred by Argon in Combination with Hypothermia in Neonatal Hypoxia–Ischemia Brain Injury

et al. 2016

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“…Hence, we investigated the mRNA levels of representative genes which, especially in the first few hours after hepatectomy (“priming phase”), are of particular importance [2,21]. Additionally, a connection to the previously proven effects of argon on these genes should exist [8,13]. …”

Section: Resultsmentioning

confidence: 99%

“…Since then, different studies have demonstrated argon's protective effect on various cells and organs. This virtue has been proven for the sensory cells of the inner ear [4] and the retina [5] and for the neuronal cells of the cerebrum [6,7,8,9], as well as for individual organ functions including kidney and heart protection [10,11,12]. However, the underlying protective mechanisms are only partly understood.…”

Section: Introductionmentioning

confidence: 99%

“…To the best of our knowledge, the organ-protective effects of the noble gas argon on the liver have not yet been investigated. Based on the literature regarding argon's protective effect on various tissues [4,5,6,7,8,9,10,11,12], our a priori hypothesis was that argon inhalation 60 min prior to partial hepatectomy (70%) has a positive effect on LR in rats.…”

Section: Introductionmentioning

confidence: 99%

“…However, the underlying protective mechanisms are only partly understood. Argon appears to influence some factors and signaling pathways - for example, interleukin-6 (IL-6), extracellular signal-regulated kinase (ERK) 1/2, tumor necrosis factor (TNF), and B-cell lymphoma 2 [8,13], which are well-known mediators of LR [2,14,15]. …”

Section: Introductionmentioning

confidence: 99%

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Argon Delays Initiation of Liver Regeneration after Partial Hepatectomy in Rats

et al. 2017

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Background: The liver can heal up to restitutio ad integrum following damage resulting from various causes. Different studies have demonstrated the protective effect of argon on various cells and organs. To the best of our knowledge, the organ-protective effects of the noble gas argon on the liver have not yet been investigated, although argon appears to influence signal paths that are well-known mediators of liver regeneration. We hypothesized that argon inhalation prior to partial hepatectomy (70%) has a positive effect on the initiation of liver regeneration in rats. Methods: Partial hepatectomy (70%) with or without inhaled argon (50 vol%) was performed for 1 h. Liver tissue was harvested after 3, 36, and 96 h to analyze the mRNA and protein expression of hepatocyte growth factor (HGF), interleukin-6 (IL-6), tumor necrosis factor-α, and extracellular signal-regulated kinase 1/2. Histological tissue samples were prepared for immunohistochemistry (bromodeoxyuridine [BrdU], Ki-67, and TUNEL) and blood was analyzed regarding the effects of argon on liver function. Statistical analyses were performed using 1-way ANOVA followed by the post hoc Tukey-Kramer test. Results: After 3 h, the primary outcome parameter of hepatocyte proliferation was significantly reduced with argon 50 vol% inhalation in comparison to nitrogen inhalation (BrdU: 15.7 ± 9.7 vs. 7.7 ± 3.1 positive cells/1,000 hepatocytes, p = 0.013; Ki-67: 17.6 ± 13.3 vs. 4.7 ± 5.4 positive cells/1,000 hepatocytes, p = 0.006). This was most likely mediated by significant downregulation of HGF (after 3 h: 5.2 ± 3.2 vs. 2.3 ± 1.0 fold, p = 0.032; after 96 h: 2.1 ± 0.5 vs. 1.3 ± 0.3 fold, p = 0.029) and IL-6 (after 3 h: 43.7 ± 39.6 vs. 8.5 ± 9.2 fold, p = 0.032). Nevertheless, we could detect no significant effect on the weight of the residual liver, liver-body weight ratio, or liver blood test results after argon inhalation. Conclusion: Impairment of liver regeneration was apparent after argon 50 vol% inhalation that was most probably mediated by downregulation of HGF and IL-6 in the initial phase. However, the present study was not adequately powered to prove that argon has detrimental effects on the liver. Further studies are needed to evaluate the effects of argon on livers with preexisting conditions as well as on ischemia-reperfusion models.

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Medical Gas Therapy for Tissue, Organ, and CNS Protection: A Systematic Review of Effects, Mechanisms, and Challenges

et al. 2022

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Gaseous molecules have been increasingly explored for therapeutic development. Here, following an analytical background introduction, a systematic review of medical gas research is presented, focusing on tissue protections, mechanisms, data tangibility, and translational challenges. The pharmacological efficacies of carbon monoxide (CO) and xenon (Xe) are further examined with emphasis on intracellular messengers associated with cytoprotection and functional improvement for the CNS, heart, retina, liver, kidneys, lungs, etc. Overall, the outcome supports the hypothesis that readily deliverable "biological gas" (CO, H 2 , H 2 S, NO, O 2 , O 3 , and N 2 O) or "noble gas" (He, Ar, and Xe) treatment may preserve cells against common pathologies by regulating oxidative, inflammatory, apoptotic, survival, and/or repair processes. Specifically, CO, in safe dosages, elicits neurorestoration via igniting sGC/cGMP/MAPK signaling and crosstalk between HO-CO, HIF-1𝜶/VEGF, and NOS pathways. Xe rescues neurons through NMDA antagonism and PI3K/Akt/HIF-1𝜶/ERK activation. Primary findings also reveal that the need to utilize cutting-edge molecular and genetic tactics to validate mechanistic targets and optimize outcome consistency remains urgent; the number of neurotherapeutic investigations is limited, without published results from large in vivo models. Lastly, the broad-spectrum, concurrent multimodal homeostatic actions of medical gases may represent a novel pharmaceutical approach to treating critical organ failure and neurotrauma.

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Argon: Systematic Review on Neuro- and Organoprotective Properties of an “Inert” Gas

Cited by 50 publications

References 39 publications

Heme Oxygenase-1 Mediates Neuroprotection Conferred by Argon in Combination with Hypothermia in Neonatal Hypoxia–Ischemia Brain Injury

Heme Oxygenase-1 Mediates Neuroprotection Conferred by Argon in Combination with Hypothermia in Neonatal Hypoxia–Ischemia Brain Injury

Argon Delays Initiation of Liver Regeneration after Partial Hepatectomy in Rats

Medical Gas Therapy for Tissue, Organ, and CNS Protection: A Systematic Review of Effects, Mechanisms, and Challenges

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