Aim: This article aimed to evaluate NITRIC OXIDE (NO) and NITRIC OXIDE synthase (iNOS) markers in patients with erosive esophagitis (EE) and those with non-erosive reflux disease (NERD) and compare them with the control group. Background: Gastro-esophageal reflux disease (GERD) is one of the most common disturbances of the upper digestive tract. Inducible NITRIC OXIDE synthase (iNOS) is expressed in esophageal adenocarcinoma. NO, the product of this enzyme, has been implicated in the pathogenesis of this condition. Nevertheless, the data on whether iNOS and NO are expressed in the early stages of GERD is conflicting. Methods: In this study, tissue samples were obtained from fifty-four patients (27 with erosive esophagitis and 27 with non-erosive reflux disease) and 27 controls. Tissue concentrations of nitrite, nitrate, and iNOS were measured using Enzyme-Linked Immunesorbent Assay (ELISA). The Bradford method was used to determine the protein concentration of samples. The results were analyzed by SPSS software (version 22. 0). In multiple comparisons, the Tukey test was performed, and p < 0. 05 was considered as the level of significance. Results Tissue amounts of iNOS were significantly higher (p= 0. 001) in EE patients compared with the control group. There was a significant difference (p= 0. 01) in this factor between EE patients and patients with NERD. Moreover, tissue levels of nitrite and nitrate were significantly higher (p = 0. 001) in patient groups compared with the control group. Conclusion: It was observed that NO and iNOS protein were increased in human esophagitis tissue. The results indicated that NITRIC OXIDE and iNOS levels are useful and effective markers in the pathogenesis of GERD. While the results are not certain, it is thought that a link exists between the expressions of iNOS and disease progression.

NITRIC OXIDE (NO), previously known as Endothelium-Derived Relaxing Factor (EDRF) is involved in a wide range of physiological and pathophysiological mechanisms. It is synthesized endogenously by the enzymes NITRIC OXIDE Synthase (NOS) in specialized tissues from its precursor L-arginine, yielding L-citrulline as a byproduct. It is released by a family of isoenzymes, viz., the endothelial (eNOS), neuronal (nNOS) and macrophage or inducible (iNOS). The three isoforms play distinct roles in the regulation of vascular tone. eNOS and nNOS are normal constituents of healthy cells, while iNOS is not usually expressed in vascular cells and its expression is seen mainly in conditions of inflammation or infection leading to overproduction of NO which acts as a killer molecule causing lethal oxidative injury. The excessive and prolonged NO generation mediated by iNOS has attracted attention. NO plays major roles in many systems, viz., cardiovascular, respiratory, renal, CNS, gastro-intestinal, immune, and so on. Hypofunctioning of NO is involved in hypertension, vasospastic diseases, impotency, gastroparesis and hypoxic pulmonary ventilation. On the other hand, hyperfunctioning is involved in diabetes, neurodegenerative diseases, epilepsy, septic shock and cerebral malaria. Phytochemicals capable of modulating NO production would exhibit potential pharmacological activities. The lecture sheds light upon the crucial role of NO in the pharmacological activities demonstrated by certain traditional herbs and phytochemicals isolated thereof. Examples of phytochemicals will be presented to illustrate their bioactivities controlled by their effect on NO production. Extracts from Hops (Humulus lupulus L.), as well as chalcones, isolated thereof, significantly inhibited NO production by suppressing the expression of iNOS. Diterpenes from Orthosiphon stamineus (used for a wide range of diseases) displayed significant inhibitory activity on NO production in LPS-activated macrophage-like J744.1 cells. The aqueous extract of red rice stimulated vascular endothelial cells to produce and/or release NO leading to endothelium-dependent relaxation. The acidic polysaccharide isolated from the ethanol-insoluble and water-soluble fraction of Panax ginseng exhibited an immunomodulating activity mediated by the production of NO and increased output of iNOS. Other selected examples will be presented in the lecture.

NITRIC OXIDE (NO) is a simple ubiquitous signaling molecule and plays important roles in almost every biological system. Recent evidences suggest that NO may act as an endocrine molecule. The aim of this review is considering available literature on endocrine roles of NO and/or its metabolites, i.e. nitrite and nitrate. Existing data suggest the idea that NO is a hormone that after production in tissues, it is stabilized and transported as nitrite and/or Snitrosothiols in the blood to target cells.