Noble Gases Therapy in Cardiocerebrovascular Diseases: The Novel Stars?

Abstract

Cardiocerebrovascular diseases (CCVDs) are the leading cause of death worldwide; therefore, to deeply explore the pathogenesis of CCVDs and to find the cheap and efficient strategies to prevent and treat CCVDs, these are of great clinical and social significance. The discovery of nitric oxide (NO), as one of the endothelium-derived relaxing factors and its successful utilization in clinical practice for CCVDs, provides new ideas for us to develop drugs for CCVDs: "gas medicine" or "medical gases." The endogenous gas molecules such as carbon monoxide (CO), hydrogen sulfide (H₂S), sulfur dioxide (SO₂), methane (CH₄), and hydrogen (H₂) have essential biological effects on modulating cardiocerebrovascular homeostasis and CCVDs. Moreover, it has been shown that noble gas atoms such as helium (He), neon (Ne), argon (Ar), krypton (Kr), and xenon (Xe) display strong cytoprotective effects and therefore, act as the exogenous pharmacologic preventive and therapeutic agents for CCVDs. Mechanistically, besides the competitive inhibition of N-methyl-D-aspartate (NMDA) receptor in nervous system by xenon, the key and common mechanisms of noble gases are involved in modulation of cell death and inflammatory or immune signals. Moreover, gases interaction and reduction in oxidative stress are emerging as the novel biological mechanisms of noble gases. Therefore, to investigate the precise actions of noble gases on redox signals, gases interaction, different cell death forms, and the emerging field of gasoimmunology, which focus on the effects of gas atoms/molecules on innate immune signaling or immune cells under both the homeostatic and perturbed conditions, these will help us to uncover the mystery of noble gases in modulating CCVDs.

Keywords: argon (Ar); cardiovascular diseases; cerebrovascular disease; gasoimmunology; helium (He); krypton (Kr); neon (Ne); xenon (Xe).

Figure 1

Noble gases have emerged as the novel preventive and therapeutic agents for cardiocerebrovascular diseases (CCVDs). The noble gas family includes helium (He), neon (Ne), argon (Ar), krypton (Kr), xenon (Xe), and the radioactive radon (Rn). They are monatomic gases at the far right of the periodic table and are chemically inert. Last but not least, it has been shown that most of noble gases have essential biological effects, including modulation of cell death, immunity/inflammation, gases interaction, and oxidative stress. They have been acted as protectants for alleviating the injuries of heart, brain, blood vessels (e.g., endothelial cells), liver, kidney, and intestine in animal models or in human body. Therefore, noble gases therapy provides a novel idea for the prevention and treatment of CCVDs.