Abstract
Carbon monoxide (CO) is generated during incomplete combustion of carbon-containing compounds and leads to acute and chronic toxicity in animals and humans depending on the concentration and exposure time. In addition to exogenous sources, CO is also produced endogenously by the activity of heme oxygenases (HOs) and the physiological significance of HO-derived CO has only recently emerged. CO exerts vasoactive, anti-proliferative, anti-oxidant, anti-inflammatory and anti-apoptotic effects and contributes substantially to the important role of the inducible isoform HO-1 as a mediator of tissue protection and host defense. Exogenous application of low doses of gaseous CO might provide a powerful tool to protect organs and tissues under various stress conditions. Experimental evidence strongly suggests a beneficial effect under pathophysiological conditions such as organ transplantation, ischemia/reperfusion, inflammation, sepsis, or shock states. The cellular and molecular mechanisms mediating CO effects are only partially characterized. So far, only a few studies in humans are available, which, however, do not support the promising results observed in experimental studies. The protective effects of exogenous CO may strongly depend on the pathological condition, the mode, time point and duration of application, the administered concentration, and on the target tissue and cell. Differences in bioavailability of endogenous CO production and exogenous CO supplementation might also provide an explanation for the lack of protective effects observed in some experimental and clinical studies. Further randomized, controlled clinical studies are needed to clarify whether exogenous application of CO may turn into a safe and effective preventive and therapeutic strategy to treat pathophysiological conditions associated with inflammatory or oxidative stress.
Highlights
High concentrations of carbon monoxide (CO) are generated during incomplete combustion of carbon-containing compounds such as wood, coal, gas, oil, or tobacco
Since tissue hypoxia is the underlying mechanism of CO-induced injury, increasing the inspired oxygen concentration represents the treatment for CO poisoning
The results from existing randomized, controlled trials of hyperbaric versus normobaric oxygen in the treatment of acute CO poisoning provide conflicting results regarding the effectiveness of hyperbaric oxygen for the prevention of neurological symptoms [12]
Summary
CO has long been regarded solely as a toxic environmental or endogenous waste product. In addition to cytoprotective properties of endogenous CO, recent evidence strongly suggests protective effects of low concentrations of exogenous CO under pathophysiological conditions such as organ transplantation, ischemia/reperfusion, inflammation, sepsis, or shock states. A potential beneficial effect of exogenous CO may highly depend on the pathological condition, the mode, time point and duration of application, the administered concentration, and on the target tissue. Further randomized, controlled clinical trials are needed to clarify whether exogenous application of CO, either by inhalation or intravenous. This article is part of a review series on Gaseous mediators, edited by Peter Radermacher. Other articles in the series can be found online at http://ccforum.com/series/gaseous_mediators application of CO-RMs, may become a safe and effective preventive and therapeutic tool to treat pathophysiological conditions associated with inflammatory or oxidative stress
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call