Noble gases xenon and argon: from cellular signalling mechanisms to organoprotection and clinical applications

BACKGROUND: Noble gases xenon (Xe) and argon (Ar) emerge as promising therapeutic agents. Extensive studies have validated their efficacy across various models of organ injury, positioning them as novel candidates for clinical translation in critical care and perioperative medicine. MAIN BODY: Xe and Ar exert protective effects through multiple mechanisms, including activation of hypoxia-inducible factor-1 (HIF-1) pathway, inhibition of regulated cell death pathways, such as apoptosis, necroptosis, ferroptosis, and pyroptosis, and suppression of pro-inflammatory signaling. By modulating these key signaling pathways, Xe and Ar have been shown to improve outcomes in neurological, cardiac, renal, and hepatic systems across diverse models of ischemia-reperfusion injury, traumatic brain injury, and systemic inflammation. Clinically, Xe has shown efficacy in anesthesia, neonatal neuroprotection, and cardiac arrest management. Ar, with greater availability and lower costs, holds promise for broader clinical use but remains in the early stage of translational research. CONCLUSION: Xe and Ar represent novel biologically active gases with the potential to provide promising therapies in perioperative and clinical care medicine. Overcoming current limitations, such as a lack of standardized delivery systems and optimized dosing strategies, is key to uncovering their clinical application.