The use of nonsteroidal anti-inflammatory drugs (NSAIDs) in combination with being physiologically stressed often occurs in in the course of different pathologies. This situation may result in the alteration of digestive system functioning. The effect of stress brings about changes in the activity of nitric oxide synthase (NOS), arginase, cyclooxygenase (COX) and lipid peroxidation, whereas the use of NSAIDs interrupts the multiple functions of the cell via the inhibition of prostaglandins (PGs) synthesis. Taking into account that NOS and COX-systems are connected in their regulation, the aim of the study was to determine the role played by NOS and lipid peroxidation under conditions of the combined action of NSAIDs and stress. In our study, male rats were used. The NSAIDs (naproxen - a non-selective COX inhibitor, celecoxib - a selective COX-2 blocker, and the compound 2A5DHT (which is the active substance of dual COX, and the lipoxygenase (LOX) inhibitor, darbufelone) were all administered at a dose 10 mg/kg, prior to water restraint stress (WRS). WRS brought about an increase of inducible NOS (iNOS) activity in the intestinal mucosal and muscular membranes, as well as in the pancreas. Because of this, constitutive NOS izoform (cNOS) and arginase activities decreased. Moreover, the MDA concentration increased, indicating the development of oxidative stress. In our work, pretreatment with naproxen, as in the WRS model, engendered a decrease in iNOS activity. What is more, administration of Celecoxib did not change iNOS activity, as compared to WRS alone, and it showed a tendency to reduce lipid peroxidation. In addition, 2A5DHT prior WRS brought about a decrease of iNOS activity, with the subsequent rise of cNOS activity. Of note, MDA concentration decreased in all studied organs, indicating the reduction of lipid peroxidation under the action of the darbufelone active substance.

The metabolic relationship between H2S and NO in gastric mucosa in norm and pathology is still poorly studied. Aim of this study was to determine mechanisms of interaction between NO and H2S generating systems under conditions of the combined actions of NSAIDs and stress. Water restraint stress (WRS) was used to induce peptic lessions in rats; naproxen and ATB-346 were administered prior to WRS. Nos2, Cbs and Ptgs2 gene expression level was determined by semiquantitative RT-PCR in gastric epitheliocytes. In the gastric mucosa were determined: alterations in H2S and NOx concentrations, changes in activity of myeloperoxidase. Both WRS and naproxen action prior to WRS cased a significant rise in myeloperoxidase activity. Administration of ATB-346 resulted in a considerable decrease of myeloperoxidase activity. Naproxen action caused the downregulation of Nos2. The level of Cbs expression in group pretreated with naproxen was much higher than in group of WRS alone. We suppose that it increases as a result of Nos2 downregulation and the correspondent decrease of NO concentration. The relationship between NO and H2S in the gastric mucosa is likely mediated through the regulation of genes expression. As a result of the released H2S, ATB-346 administration decreased the severity of gastric mucosa lesions.

The aim of this study was to assess the level of nitric oxide production and arginase activity in patients with arterial hypertension and type II diabetes mellitus during infection with SARS-CoV-2. The study groups included patients with arterial hypertension, patients with arterial hypertension combined with a severe course of COVID-19 and patients who, in addition to arterial hypertension and COVID-19, were suffering from type II diabetes mellitus. The volunteers without any clinical signs of diseases and normal blood pressure formed the control group. It has been established that arterial hypertension, combined with COVID-19 occurs along with reduced L-arginine, nitric oxide, superoxide dismutase activity and increased arginase activity. At the same time, the presence of arterial hypertension in patients with diabetes and coronavirus disease is accompanied by a decline in the content of L-arginine and arginase activity. Our study’s results may help scientists find new pharmacological targets in the future treatment of coronavirus disease and comorbid disorders. Keywords: arginase, COVID-19, diabetes mellitus, hypertension, L-arginine, nitric oxide, superoxide dismutase

Serotonin (5-hydroxytryptamine, 5-HT) plays an important role in the regulation of the functioning of the gastrointestinal tract, including that of the colon. The response of smooth muscles, blood vessels and colon mucosa (CM) to 5-HT is realized through the activation of various types of 5-HT receptors, in particular, 5-HT4 receptors, since the latter are identified on colon cells membranes (enterocytes, smooth muscles and endothelium). The aim of our study was to determine the effect of 5-НT4 receptors agonist (mosapride) on nitrogen (II) oxide production and lipid peroxidation in CM and colon muscle tissue (CMT) under the conditions of experimental ulcerative colitis (UC).