Abstract
Carbon monoxide (CO) has long been considered a purely toxic by-product of incomplete combustion processes. Acute exposure to high concentrations of CO is one of the leading causes of fatal poisoning in industrial countries. However, after two decades of intensive research, there is ample evidence that CO endogenously produced by heme oxygenase enzymes has essential physiological functions and is of vital importance for cellular hemostasis. Furthermore, exogenously applied CO in low concentrations mediates potent cytoprotective effects. An overwhelming number of different in vitro and in vivo models demonstrated the protective action of CO application, e.g., in ischemia/reperfusion, transplantation, oxidative stress, inflammation, and others. Protection by this gaseous molecule could be illustrated for most organs, most species, and for different routes of administration. Now being on the verge of entering clinical trials, the question emerges whether the administration of low-dose CO would be safe for patients when used as a potential therapeutic. Therefore, this review summarizes in particular toxicological data obtained from low-dose CO exposure and discusses its impact on a possible clinical application.
Keywords: Carbon monoxide, toxicity, heme oxygenase, HO-1, organ protection, stress response
Current Pharmaceutical Biotechnology
Title:Carbon Monoxide - Toxicity of Low-Dose Application
Volume: 13 Issue: 6
Author(s): Rene Schmidt, Helen Ryan and Alexander Hoetzel
Affiliation:
Keywords: Carbon monoxide, toxicity, heme oxygenase, HO-1, organ protection, stress response
Abstract: Carbon monoxide (CO) has long been considered a purely toxic by-product of incomplete combustion processes. Acute exposure to high concentrations of CO is one of the leading causes of fatal poisoning in industrial countries. However, after two decades of intensive research, there is ample evidence that CO endogenously produced by heme oxygenase enzymes has essential physiological functions and is of vital importance for cellular hemostasis. Furthermore, exogenously applied CO in low concentrations mediates potent cytoprotective effects. An overwhelming number of different in vitro and in vivo models demonstrated the protective action of CO application, e.g., in ischemia/reperfusion, transplantation, oxidative stress, inflammation, and others. Protection by this gaseous molecule could be illustrated for most organs, most species, and for different routes of administration. Now being on the verge of entering clinical trials, the question emerges whether the administration of low-dose CO would be safe for patients when used as a potential therapeutic. Therefore, this review summarizes in particular toxicological data obtained from low-dose CO exposure and discusses its impact on a possible clinical application.
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Cite this article as:
Schmidt Rene, Ryan Helen and Hoetzel Alexander, Carbon Monoxide - Toxicity of Low-Dose Application, Current Pharmaceutical Biotechnology 2012; 13 (6) . https://dx.doi.org/10.2174/138920112800399103
DOI https://dx.doi.org/10.2174/138920112800399103 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
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