The therapeutic potential of carbon monoxide

  title={The therapeutic potential of carbon monoxide},
  author={Roberto Motterlini and Leo E. Otterbein},
  journal={Nature Reviews Drug Discovery},
Carbon monoxide (CO) is increasingly being accepted as a cytoprotective and homeostatic molecule with important signalling capabilities in physiological and pathophysiological situations. The endogenous production of CO occurs through the activity of constitutive (haem oxygenase 2) and inducible (haem oxygenase 1) haem oxygenases, enzymes that are responsible for the catabolism of haem. Through the generation of its products, which in addition to CO includes the bile pigments biliverdin… 
Carbon monoxide: a new pharmaceutical agent?
Small amounts of carbon monoxide (CO) are continuously produced in mammals. The intracellular levels of this gaseous molecule can markedly increase under stressful conditions following the induction
Therapeutic potential of carbon monoxide in multiple sclerosis
The accumulating data discussed herein support the possibility that CORMs may represent a novel class of drugs with disease‐modifying properties in multiple sclerosis.
Therapeutic Aspects of Carbon Monoxide in Cardiovascular Disease
This review highlights the mechanism of the biological effects of CO and its potential application as a therapeutic in clinical settings, including in cardiovascular diseases, and discusses the obstacles and limitations of using exogenous CO or CORMs as a therapy option, with respect to acute CO poisoning.
The role of carbon monoxide as a gasotransmitter in cardiovascular and metabolic regulation
This chapter provides an overview of the many roles CO plays as a gasotransmitter in the cardiovascular system, including regulating blood pressure, smooth muscle cell proliferation, anti-inflammatory,Anti- apoptotic, and anti-coagulation effects.
Biological signaling by carbon monoxide and carbon monoxide-releasing molecules.
How the binding of CO with key ferrous hemoproteins serves as a posttranslational modification that regulates important processes as diverse as aerobic metabolism, oxidative stress, and mitochondrial bioenergetics is discussed.
Therapeutic Applications of Carbon Monoxide
The aim of this review is to discuss the potential therapeutic implications of CO with a focus on lung injury and sepsis-related models and co-treatment and post-treatment with CO.
Carbon monoxide: a vital signalling molecule and potent toxin in the myocardium.
Carbon monoxide and the CNS: challenges and achievements
The role of exogenous and endogenous CO (via HO activity and expression) in various CNS pathologies is focused upon, based upon data from experimental models, as well as from some clinical data on human patients.
Strategies toward Organic Carbon Monoxide Prodrugs.
This Account describes the work in this area as well as the demonstration for these organic CO prodrugs to recapitulate CO's pharmacological effects both in vitro and in vivo and proposes a new concept of "enrichment triggered CO release" by conjugating both components with a mitochondria-targeting moiety to achieve targeted CO delivery with improved biological outcomes.


Therapeutic applications of carbon monoxide-releasing molecules
A novel class of substances, CO-releasing molecules (CO-RMs), which are capable of exerting a variety of pharmacological activities via the liberation of controlled amounts of CO in biological systems are identified.
Antimicrobial Action of Carbon Monoxide-Releasing Compounds
The results constitute the first evidence that CO can be utilized as an antimicrobial agent and are expected to be the starting point for the development of novel types of therapeutic drugs designed to combat antibiotic-resistant pathogens, which are widespread and presently a major public health concern.
Use of carbon monoxide as a therapeutic agent: promises and challenges
Although in its infancy and far from being used for clinical applications, the CO-RMs technology is supported by very encouraging biological results and reflected by the chemical versatility of these compounds and their endless potential to be transformed into CO-based pharmaceuticals.
Bioactivity and pharmacological actions of carbon monoxide-releasing molecules.
The data presented in this review corroborate the notion that transition metal carbonyls could be used as carriers to deliver CO in mammals and highlight the bioactivity and potential therapeutic features of CO-RMs in the mitigation of cellular and organ dysfunction.
Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications.
The molecular and biochemical characterization of HOs is reviewed, with a discussion on the mechanisms of signal transduction and gene regulation that mediate the induction of HO-1 by environmental stress, to lay a foundation for potential future clinical applications of these systems.
Heme oxygenase and carbon monoxide initiate homeostatic signaling
The manner in which CO exposure alone modulates the molecular machinery of the cell so that a subsequent stress stimulus will elicit a homeostatic response as opposed to one that is chaotic and disordered is highlighted.
Bench-to-bedside review: Carbon monoxide – from mitochondrial poisoning to therapeutic use
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.
Biological chemistry of carbon monoxide.
  • C. Piantadosi
  • Chemistry, Biology
    Antioxidants & redox signaling
  • 2002
A brief update on the biochemistry of CO as it relates to Hp binding, chemical oxidative processes, and cellular function is provided.
Carbon monoxide signals via inhibition of cytochrome c oxidase and generation of mitochondrial reactive oxygen species
  • B. Zuckerbraun, B. Chin, L. Otterbein
  • Biology, Chemistry
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2007
It is shown that CO increases ROS generation in RAW 264.7 cells, which is inhibited by antimycin A and is absent in respiration‐deficient p° cells, and the hypothesis that CO acts via inhibition of cytochrome c oxidase leading to the generation of low levels of reactive oxygen species (ROS) is tested.