Gaseous mediator

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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]

Contents

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. PMID   26319186.
  4. Sulaieva, O. N.; Wallace, J. L. (2016). "New strategy for gastrointestinal protection based on gaseous mediators application". Russian Journal of Gastroenterology, Hepatology, Coloproctology. 26 (3): 17–23. doi: 10.22416/1382-4376-2016-26-3-17-23 . Retrieved 2020-04-27.
  5. 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.
  6. 1 2 Diaz Soto, Juan C.; Nabzdyk, Christoph G.S. (2023). "Running on (Too Many) Fumes? Gaseous Mediators in Septic Shock" . Chest Journal. 163 (2): 262–263. doi:10.1016/j.chest.2022.10.012. PMID   36759109.