Gaseous mediator

Gaseous mediators are chemicals that are produced in small amounts by some cells of the mammalian body and have a number of biological signalling functions. There are three so-far-identified gaseous mediator molecules: nitric oxide (NO), hydrogen sulfide (H₂S), and carbon monoxide (CO).[1]

Clinical applications

Endogenous gaseous mediators have shown anti-inflammatory and cytoprotective properties[2] Combination nonsteroidal anti-inflammatory drugs featuring both a cyclooxygenase inhibitor and gaseous mediator releasing component are being investigated as a safer alternative to current anti-inflammatory drugs[3] due to their potential reduction in risk for gastrointestinal ulcer formation.[4]

Role of gaseous mediators during septic shock

When septic shock occurs in the human body due to bacterial toxins, nitric oxide is released by a variety of cells through the expression of inducible nitric oxide synthase in order to induce vasodilation as part of the inflammatory response.[5] The released nitric oxide can be crucial to the body by reducing instances of platelet and leukocyte adhesion while also counteracting apoptosis.[6] However, prolonged septic shock could lead to the overproduction of nitric oxide, which could lead to cell damage due to nitric oxide radical formation and peroxynitrite (ONOO^−) formation after interacting with oxygen in the body.[5] In order to alleviate the toxic effects caused by overproduction of nitric oxide during septic shock, a single high dose (5g IV) of Vitamin B12 has shown the potential to inhibit nitric oxide synthase while acting as a radical scavenger that assists in the elimination of excess nitric oxide produced during prolonged septic shock.[6]

References

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.