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Nitric oxide is a colorless gas with the formula NO. It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its chemical formula. Nitric oxide is also a heteronuclear diatomic molecule, a class of molecules whose study spawned early modern theories of chemical bonding.
Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel walls are composed of endothelial tissue and a basal membrane lining the lumen of the vessel, concentric smooth muscle layers on top of endothelial tissue, and an adventitia over the smooth muscle layers. Relaxation of the smooth muscle layer allows the blood vessel to dilate, as it is held in a semi-constricted state by sympathetic nervous system activity. Vasodilation is the opposite of vasoconstriction, which is the narrowing of blood vessels.
Agmatine, also known as 4-aminobutyl-guanidine, was discovered in 1910 by Albrecht Kossel. It is a chemical substance which is naturally created from the amino acid arginine. Agmatine has been shown to exert modulatory action at multiple molecular targets, notably: neurotransmitter systems, ion channels, nitric oxide (NO) synthesis, and polyamine metabolism and this provides bases for further research into potential applications.
Nitric oxide synthases (NOSs) are a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine. NO is an important cellular signaling molecule. It helps modulate vascular tone, insulin secretion, airway tone, and peristalsis, and is involved in angiogenesis and neural development. It may function as a retrograde neurotransmitter. Nitric oxide is mediated in mammals by the calcium-calmodulin controlled isoenzymes eNOS and nNOS. The inducible isoform, iNOS, involved in immune response, binds calmodulin at physiologically relevant concentrations, and produces NO as an immune defense mechanism, as NO is a free radical with an unpaired electron. It is the proximate cause of septic shock and may function in autoimmune disease.
Heme oxygenase, or haem oxygenase, is an enzyme that catalyzes the degradation of heme to produce biliverdin, ferrous iron, and carbon monoxide.
Gasotransmitters is a class of neurotransmitters. The molecules are distinguished from other bioactive endogenous gaseous signaling molecules based on a need to meet distinct characterization criteria. Currently, only nitric oxide, carbon monoxide, and hydrogen sulfide are accepted as gasotransmitters. According to in vitro models, gasotransmitters, like other gaseous signaling molecules, may bind to gasoreceptors and trigger signaling in the cells.
Endothelial NOS (eNOS), also known as nitric oxide synthase 3 (NOS3) or constitutive NOS (cNOS), is an enzyme that in humans is encoded by the NOS3 gene located in the 7q35-7q36 region of chromosome 7. This enzyme is one of three isoforms that synthesize nitric oxide (NO), a small gaseous and lipophilic molecule that participates in several biological processes. The other isoforms include neuronal nitric oxide synthase (nNOS), which is constitutively expressed in specific neurons of the brain and inducible nitric oxide synthase (iNOS), whose expression is typically induced in inflammatory diseases. eNOS is primarily responsible for the generation of NO in the vascular endothelium, a monolayer of flat cells lining the interior surface of blood vessels, at the interface between circulating blood in the lumen and the remainder of the vessel wall. NO produced by eNOS in the vascular endothelium plays crucial roles in regulating vascular tone, cellular proliferation, leukocyte adhesion, and platelet aggregation. Therefore, a functional eNOS is essential for a healthy cardiovascular system.
Cyclooxygenase 1 (COX-1), also known as prostaglandin-endoperoxide synthase 1, is an enzyme that in humans is encoded by the PTGS1 gene. In humans it is one of three cyclooxygenases.
COX-inhibiting nitric oxide donators (CINODs), also known as NO-NSAIDs, are a new class of nonsteroidal anti-inflammatory drug (NSAID) developed with the intention of providing greater safety than existing NSAIDs.
Biological functions of nitric oxide are roles that nitric oxide plays within biology.
Nitrotyrosine is a product of tyrosine nitration mediated by reactive nitrogen species such as peroxynitrite anion and nitrogen dioxide. Nitrotyrosine is identified as an indicator or marker of cell damage, inflammation as well as NO (nitric oxide) production. Nitrotyrosine is formed in the presence of the active metabolite NO. Generally in many disease states, oxidative stress increases the production of superoxide (O2−) and NO forming peroxynitrite (ONOO−) a destructive free radical oxidant. The production of ONOO− is capable of oxidizing several lipoproteins and of nitrating tyrosine residues in many proteins. It is difficult to determine the production of ONOO− so, usually nitrotyrosine in proteins are the detectable marker for indirectly detecting ONOO−. It is detected in large number of pathological conditions and is considered a marker of NO-dependent, reactive nitrogen species-induced nitrative stress. Nitrotyrosine is detected in biological fluids such as plasma, lung aspirants-BALF (Broncho alveolar lining fluid) and urine. Increased level of nitrotyrosine is detected in rheumatoid arthritis, septic shock and coeliac disease. In all these studies nitrotyrosine was undetected in healthy subjects. Nitrotyrosine is also found in numerous other disease-affected tissues, such as the cornea in keratoconus. Peroxynitrite and/or nitrative stress may participate in the pathogenesis of diabetes.
Antibe Therapeutics was a Toronto-based pharmaceutical company that develops pain and inflammation-reducing drugs based on gaseous mediator technology. Antibe was founded by John L. Wallace, also a co-founder of NicOx, the first company to develop drugs utilizing gaseous mediators. Founded in 2009, the company listed on the TSX Venture Exchange in 2013 and was moved to the Toronto Stock Exchange in November 2020. In 2015, Antibe acquired Citagenix, a distributor involved in regenerative medicine.
NOSH-Aspirin is a category of new hybrids of acetylsalicylic acid, bearing both nitric oxide (NO)- and hydrogen sulfide (H2S)- releasing areas. Preliminary studies have found that four NOSH variants, evaluated in eleven different human cancer cell lines, were effective in inhibiting the growth of these cell lines. NOSH-1 was also devoid of any cellular toxicity, and was comparable to aspirin in its anti-inflammatory properties.
Nitric Oxide is a peer-reviewed scientific journal and official journal of the Nitric Oxide Society. The journal covers the broad field of nitric oxide and other similar gaseous signaling molecules such as hydrogen sulfide and carbon monoxide. Published research includes basic and clinical topics such as cell biology, molecular biology, biochemistry, immunology, pathology, genetics, physiology, pharmacology, and disease processes.
Diallyl trisulfide (DATS), also known as Allitridin, is an organosulfur compound with the formula S(SCH2CH=CH2)2. It is one of several compounds produced by hydrolysis of allicin, including diallyl disulfide and diallyl tetrasulfide; DATS is one of the most potent.
Carbon monoxide-releasing molecules (CORMs) are chemical compounds designed to release controlled amounts of carbon monoxide (CO). CORMs are being developed as potential therapeutic agents to locally deliver CO to cells and tissues, thus overcoming limitations of CO gas inhalation protocols.
Gaseous signaling molecules are gaseous molecules that are either synthesized internally (endogenously) in the organism, tissue or cell or are received by the organism, tissue or cell from outside and that are used to transmit chemical signals which induce certain physiological or biochemical changes in the organism, tissue or cell. The term is applied to, for example, oxygen, carbon dioxide, sulfur dioxide, nitrous oxide, hydrogen cyanide, ammonia, methane, hydrogen, ethylene, etc.
Hydrogen sulfide is produced in small amounts by some cells of the mammalian body and has a number of biological signaling functions. Only two other such gases are currently known: nitric oxide (NO) and carbon monoxide (CO).
Otenaproxesul is a analgesic and anti-inflammatory drug being developed by Antibe Therapeutics. An NSAID structurally derived from naproxen, in 2016 it received approval to commence phase II clinical trials as a treatment for osteoarthritis after completing phase I clinical trials in 2015. In 2018, the drug completed trials for gastrointestinal safety, and in 2020 completed phase IIb trials on efficacy of pain reduction. Initial phase III clinical trials in 2021 failed to meet the necessary criteria to advance to the next phase.
Csaba Szabo, a physician and pharmacologist, is the Head of the Pharmacology Section and President of the Department of Oncology, Microbiology and Immunology (OMI) of the University of Fribourg in Switzerland. The Public Library of Science Magazine, PLOS Biology, recognized Szabo in 2019 as one of the most cited researchers in the world.
References
- ↑ Leffler, C. W.; Parfenova, H; Jaggar, J. H.; Wang, R (March 2006). "Carbon monoxide and hydrogen sulfide: gaseous messengers in cerebrovascular circulation". J. Appl. Physiol. 100 (3): 1065–76. doi:10.1152/japplphysiol.00793.2005. PMC 1363746 . PMID 16467393.
- ↑ Rodrigues, L.; Ekundi-Valentim, E.; Florenzano, J.; Cerqueira, A. R. A.; Soares, A. G.; Schmidt, T. P.; Santos, K. T.; Teixeira, S. A.; Ribela, M. T. C. P.; Rodrigues, S. F.; de Carvalho, M. H. (2017-01-01). "Protective effects of exogenous and endogenous hydrogen sulfide in mast cell-mediated pruritus and cutaneous acute inflammation in mice". Pharmacological Research. 115: 255–266. doi:10.1016/j.phrs.2016.11.006. hdl: 10871/24576 . ISSN 1043-6618. PMID 27840098. S2CID 1165855.
- ↑ Sulaieva, Oksana; Wallace, John L (2015-12-01). "Gaseous mediator-based anti-inflammatory drugs". Current Opinion in Pharmacology. Gastrointestinal • Endocrine and metabolic diseases. 25: 1–6. doi:10.1016/j.coph.2015.08.005. ISSN 1471-4892.
- ↑ Sulaieva, O. N.; Wallace, J. L. (2016). "New strategy for gastrointestinal protection based on gaseous mediators application". Russian Journal of Gastroenterology, Hepatology, Coloproctology. Retrieved 2020-04-27.
- 1 2 Hermann, Anton; Sitdikova, Guzel F.; Weiger, Thomas M., eds. (2012). Gasotransmitters: Physiology and Pathophysiology. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 18–19. doi:10.1007/978-3-642-30338-8. ISBN 978-3-642-30337-1.
- 1 2 Diaz Soto, Juan C.; Nabzdyk, Christoph G.S. "Running on (Too Many) Fumes? Gaseous Mediators in Septic Shock". CHEST Journal. 163 (2): 262–263. doi:10.1016/j.chest.2022.10.012.