Can tissue nitric oxide synthesis 2 (iNOS) levels play a role in the pathophysiology of reflux esophagitis?
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Abstract
Objective: Nitric oxide (NO) is a strong dilatator, playing an important role in inflammatory events. Its production is regulated by NO synthase 2 (NOS2/iNOS). Our aim was to compare iNOS in esophageal tissues of patients with erosive or non-erosive reflux esophagitis to that of normal cases.
Materials and Methods: The study was conducted in 2019–2020 on patients undergoing upper gastrointestinal (UGI) endoscopy. Study included 30 patients who had no reflux symptoms and were not diagnosed with reflux esophagitis in the UGI endoscopy (control), 22 who had pronounced reflux symptoms but could not be diagnosed with reflux esophagitis in the endoscopy (non-erosive reflux), and 51 who had reflux esophagitis in the endoscopy (erosive reflux esophagitis). Using the enzyme-linked immunosorbent assay, tissue iNOS levels were assessed on samples from the lower end of the esophagus.
Results: Average iNOS level was 5.02±1.51 picogram/milliliter (pg/mL) in the normal group and 5.04±1.68 pg/mL in all reflux esophagitis cases. iNOS levels were higher in non-erosive reflux and lower in erosive reflux than in controls. In erosive reflux A, B, and C, iNOS levels were 5.03±1.64, 5.10±2.23, and 4.06±0.02 pg/mL, respectively. The level in erosive reflux C is considerably lower than in the normal group. However, none of the differences between the groups was significant.
Conclusions: NO synthase was higher in patients with non-erosive reflux esophagitis and considerably lower in those with erosive reflux C, compared to the normal cases. Although not significant, the differences suggest that NO and iNOS levels may be important in reflux physiopathology.
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Accepted 2021-07-25
Published 2021-07-26
References
Kahrilas PJ. Gastroesophageal reflux disease. Jama. 1996;276(12):983–8. doi: 10.1001/jama.1996.03540120061035
Orlando RC. Reflux esophagitis: overview. Scand J Gastroenterol. 1995;30(sup210):36–7. doi: 10.3109/00365529509090267
Nebel OT, Fornes MF, Castell DO. Symptomatic gastroesophageal reflux: incidence and precipitating factors. Am J Dig Dis. 1976;21(11):953–6. doi: 10.1007/BF01071906
Locke 3rd GR, Talley NJ, Fett SL, Zinsmeister AR, Melton 3rd LJ. Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmsted County, Minnesota. Gastroenterology. 1997;112(5):1448–56. doi: 10.1016/S0016-5085(97)70025-8
Vakil N, Van Zanten SV, Kahrilas P, Dent J, Jones R, the Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006;101(8):1900–20. doi: 10.1111/j.1572-0241.2006.00630.x
Goyal RK. Diseases of the esophagus. In: Longo DL, Fauci AS, editors. Harrison's Gastroenterology and Hepatology. New York: McGraw-Hill Medical; 2010. p. 112–24
Palmieri EM, McGinity C, Wink DA, McVicar DW. Nitric oxide in macrophage immunometabolism: hiding in plain sight. Metabolites. 2020;10(11):429. doi: 10.3390/metabo10110429
Lind M, Hayes A, Caprnda M, Petrovic D, Rodrigo L, Kruzliak P, et al. Inducible nitric oxide synthase: good or bad? Biomed Pharmacother. 2017;93(September):370–5. doi: 10.1016/j.biopha.2017.06.036
Kleinert H, Pautz A, Linker K, Schwarz PM. Regulation of the expression of inducible nitric oxide synthase. Eur J Pharmacol. 2004;500(1-3):255–66. doi: 10.1016/j.ejphar.2004.07.030
Kowalczyk E, Kopff A, Kopff M, Błaszczyk J, Fijałkowski P, Kowalski J. Nitric oxide metabolism. Wiad Lek. 2006;59(11-12):889–93
Aktan F. iNOS-mediated nitric oxide production and its regulation. Life Sci. 2004;75(6):639–53. doi: 10.1016/j.lfs.2003.10.042
Lee M, Rey K, Besler K, Wang C, Choy J. Immunobiology of nitric oxide and regulation of inducible nitric oxide synthase. In: Kloc M, editor. Macrophages. Results and Problems in Cell Differentiation. 62. Cham, Switzerland: Springer; 2017. p. 181–207
MacMacking J, Xie Q, Nathan C. Nitric oxide and macrophages function. Annu Rev Immunol. 1997;15:323–50. doi: 10.1146/annurev.immunol.15.1.323
Ferguson HR, Wild CP, Anderson LA, Murphy SJ, Johnston BT, Murray LJ, et al. Cyclooxygenase-2 and inducible nitric oxide synthase gene polymorphisms and risk of reflux esophagitis, Barrett's esophagus, and esophageal adenocarcinoma. Cancer Epidemiol Biomarkers Prev. 2008;17(3):727–31. doi: 10.1158/1055-9965.EPI-07-2570
McAdam E, Haboubi HN, Forrester G, Eltahir Z, Spencer-Harty S, Davies C, et al. Inducible nitric oxide synthase (iNOS) and nitric oxide (NO) are important mediators of reflux-induced cell signalling in esophageal cells. Carcinogenesis. 2012;33(11):2035–43. doi: 10.1093/carcin/bgs241
Inamori M, Shimamura T, Nagase H, Abe Y, Umezawa T, Nakajima A, et al. mRNA expression of inducible nitric oxide synthase, endothelial nitric oxide synthase and vascular endothelial growth factor in esophageal mucosa biopsy specimens from patients with reflux esophagitis. Hepatogastroenterology. 2006;53(69):361–5
Soeters PB, Hallemeesch MM, Bruins MJ, Van Eijk HMH, and Deutz NEP. Quantitative in vivo assessment of arginine utilization and nitric oxide production in endotoxemia. Am J Surg. 2002;183(4):480–488.