Carbon Monoxide as a Molecular Modulator of Ischemia-Reperfusion Injury: New Insights for Translational Application...

Carbon monoxide (CO) is generally recognized as a toxic gas; however, it has recently been identified as an endogenous gasotransmitter with significant cytoprotective properties. CO modulates key molecular pathways, including anti-inflammatory, anti-apoptotic, antioxidant, and vasodilatory signaling pathways, by targeting heme- and non-heme-containing proteins. These proteins include soluble guanylate cyclase, cytochrome P450 enzymes, MAPKs, and NLRP3. This review summarizes recent advances in understanding the molecular mechanisms associated with the protective effects of CO, particularly in the context of ischemia-reperfusion injury relevant to organ transplantation. We discuss preclinical data from rodent and large animal models, as well as therapeutic delivery strategies, such as inhalation, CO-releasing molecules, and gas-entrapping materials. We also reviewed early-phase clinical trials. The objective of this review is to provide a thorough exploration of CO as a potential therapeutic gas, with special emphasis on its application in transplantation.