CHARACTERISTIC OF MECHANISMS OF ANTIULCEROGENIC ACTION OF AGENTS OF VANILLOID RECEPTORS (TRPV1) ON THE MODEL OF GASTROPATHY INDUCED BY ACETYLSALICYLIC ACID

One of the main problems of the use of acetylsalicylic acid (ASA) is its withdrawal or initial “non-prescription” resulted from the prior developed or potential side effects in the gastrointestinal tract. In this case, the reasons for the abolition of ASA are not only serious complications in the form of gastrointestinal bleeding or perforations, but
also dyspeptic phenomena that are accompanied by the ongoing development of aspirin-induced gastroenteropathy. The aim of the study. To characterize the mechanisms of antiulcerogenic action of agonist TRPV1 (transient receptor potential vanilloid 1) vanillin (100 mg/kg) on the model of subchronic ASA-induced gastropathy in rats. Materials and methods. The study was performed on 35 mature male rats. Gastropathy induced by ASA was simulated by a fiveday intragastric (i.g.) introduction via the orogastric probe of an ASA suspension of 150 mg/kg/ day during 5 days. Omeprazole (50 mg/kg, i.g.) and vanillin (100 mg/kg, i.g.) were administered in the form of suspensions 60 minutes prior to the use of ASA. The concentration of malonic dialdehyde, and the activity of catalase were determined in the homogenates of gastric mucosa. The prooxidant/antioxidant ratio (ProAntidex) was calculated dased on the ratio of catalase activity (mcat/kg) and the concentration of malondialdehyde (MDA concentration (umol/kg). The content of NO metabolites in the stomach tissues was determined by the method of Miranda K.M. et al. Results and discussion. Preventive prophylactic use of vanillin (100 mg/kg) leads to the decrease in the intensity of processes of lipid peroxidation in the gastric mucosa caused by the action of ASA (150 mg/kg). This was indicated by a statistically significant (p≤0.05) decrease of 26.4% in MDA content and an increase in catalase activity by 29.0% relatively to those animals
with ASA-induced gastropathy without correction. Also, the use of vanillin resulted in a statistically significant (p≤0.05) increase in the content of NO metabolites by 68.0% (841.4 ± 35.95 umol / g) relatively to the animals of the control group. With the combined use of vanillin and omeprazole, a statistically significant (p≤0.05) absolute normalization of the NO metabolite level (927.4 ± 34.78 mmol/g) in the gastric mucosa was established, which corresponded to the indices of intact animals. Conclusion. The study showed that the activation of vanilloid (capsaicinoid) receptors due to the use of TRPV1 agonist, in particular vanillin, can reduce deistvie ulcerogenic NSAID, including ASA, that allows to consider the TRPV1 agonists as a new class gastroprotective drugs.

vanillin, acetylsalicylic acid, ulcerogenicity, nitric oxide

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