Carbon monoxide: Mechanisms of action and potential clinical implications

Abstract

Small amounts of carbon monoxide (CO) are continuously produced in mammals. The intracellular levels of CO can increase under stressful conditions following the induction of HO-1 (heme oxygnase-1), a ubiquitous enzyme responsible for the catabolism of heme. Unlike nitric oxide, which is a free radical, CO does not contain free electrons but may be involved in oxidative stress. The carbonate radical has been proposed to be a key mediator of oxidative damage resulting from peroxynitrite production, likewise, the precursor of the carbonate radical anion being bicarbonate and carbon dioxide. We report herein some of the transcription factors and protein kinases involved in the regulation of vascular HO-1 expression. Beyond its widely feared toxicity, CO has revealed a very important biological activity as a signaling molecule with marked protective actions namely against apoptosis and endothelial oxidative damage. Abnormal metabolism and function of CO contribute to the pathogenesis and development of cardiovascular diseases. Important results have been reported in which CO and CO-releasing molecules (CO-RMs) prevent intimal hyperplasia by arresting hyperproliferative vascular smooth muscle cells and increased mobilization and recruitment of bone-marrow-derived progenitor cells. Clinical studies have demonstrated beneficial properties of CO-RMs in transplantation. The anti-inflammatory properties of CO and CO-RMs have been demonstrated in a multitude of animal models of inflammation, suggesting a possible therapeutic application for inflammatory diseases. The development of a technology concerning CO-RMs that controls the delivery and action of CO under different pathological conditions represents a major step forward in the development of CO-based pharmaceuticals with therapeutic applications.

Obesity does not affect the healing of femur fractures in mice

“…Moreover, accumulating evidence indicates that HO-1 downregulates inflammatory processes in a variety of tissues [46]. In the present study the expression of HO-1 within the callus tissue of HFD-fed animals was found significantly reduced.…”

Pathophysiological Mechanisms in Gaseous Therapies for Severe Malaria

“…Although widely known for its toxicity due to its high-affinity binding to hemoglobin, CO has drawn scientific attention for its role as a signaling molecule in the gastrointestinal tract, a paracrine mediator of smooth muscle hyperpolarization, and an immunomodulatory effector (35)(36)(37). The immune actions of CO take part in the "immunological web" of HO-1, the inducible form of heme oxygenase, whose expression is upregulated in situations of cellular exposure to oxidant agents, pathogens, and other stressors (35).…”

The effects of homocysteine and nitric oxide inhibitor, applied separately and simultaneously, on acetylcholinesterase activity in the rat heart tissue

“…Hemoksigenaza ima tri izoenzima: hemoksigenazu 1 (HO-1), hemoksigenazu 2 (HO-2) i hemoksigenazu 3 (HO-3). Hemoksigenaza 1 je inducibilni enzim, dok su HO-2 i HO-3 konstitutivni (15). Povećana ili smanjena ekspresija HO prisutna je kao jedan od patofizioloških mehanizama u mnogim bolestima, kao što su Alchajmerova i Parkinsonova bolest, povišen krvni pritisak, hipertrofija srca, hronična srčana insuficijencija itd.…”