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


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Abstract

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, butalso 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 animalswith 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.

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Pharmacy & Pharmacology V. 5 N 3, 2017Фармация и фармакология Т. 5 № 3, 2017Фармакология, клиническая фармакология harmacology, PharmacologyPharmacy & Pharmacology V. 5 N 3, 2017Фармация и фармакология Т. 5 № 3, 2017Фармакология, клиническая фармакология harmacology, Pharmacology
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About the authors

F. V. Hladkykh

State institution «Grigoriev Institute for medical Radiology The National Academy of Medical Sciences of Ukraine»

Email: fedir.hladkykh@gmail.com

References

  1. Шахматова О.О., Комаров А.Л. АЦЕТИЛСАЛИЦИЛОВАЯ КИСЛОТА. ПОСЛЕДНИЕ НОВОСТИ О ДОЗАХ, ЭФФЕКТИВНОСТИ И БЕЗОПАСНОСТИ ДЛИТЕЛЬНОГО ЛЕЧЕНИЯ // Атмосфера. Новости кардиологии. 2011. № 3. С. 2–10.
  2. Shim Y. K., Kim N. NONSTEROIDAL ANTI-INFLAMMATORY DRUG AND ASPIRIN-INDUCED PEPTIC ULCER DISEASE // Korean J. Gastroenterol. 2016. No. 67. Р. 300–312. doi: 10.4166/kjg.2016.67.6.300
  3. Baigent C., Sudlow C., Collins R., Peto R. COLLABORATIVE META ANALYSIS OF RANDOMISED TRIALS OF ANTIPLATELET THERAPY FOR PREVENTION OF DEATH, MYOCARDIAL INFARCTION, AND STROKE IN HIGH RISK PATIENTS: ANTITHROMBOTIC TRIALISTS’ COLLABORATION // British Medical Journal. 2002. No. 324. Р. 71–86. doi: 10.1136/bmj.324.7329.71
  4. Sung J.J., Lau J.Y., Ching J.Y., Wu J.C., Lee Y.T., Chiu P.W., Leung V.K., Wong V.W., Chan F.K. CONTINUATION OF LOW-DOSE ASPIRIN THERAPY IN PEPTIC ULCER BLEEDING // Annals of Internal Medicine. 2010. Vol. 152. No. 1. Р. 1–10. doi: 10.7326/0003-4819-152-1-201001050-00179
  5. Гладких Ф. В., Степанюк Н.Г. ВІНБОРОН: ПЕРШИЙ УКРАЇНСЬКИЙ ГАСТРОПРОТЕКТОР – АГОНІСТ ВАНІЛОЇДНИХ РЕЦЕПТОРІВ (TRPV1) // Фармакологія та лікарська токсикологія. 2016. № 4–5 (50). С. 20–29. URL: http://pharmtox-j.org.ua/webfm_send/523
  6. Зуфаров П. С., Якубов А.В., Салаева Д.Т. СРАВНИТЕЛЬНАЯ ОЦЕНКА ЭФФЕКТИВНОСТИ ОМЕПРАЗОЛА И ПАНТОПРАЗОЛА ПРИ ЛЕЧЕНИИ ГАСТРОПАТИИ, ВЫЗВАННОЙ НЕСТЕРОИДНЫМИ ПРОТИВОВОСПАЛИТЕЛЬНЫМИ СРЕДСТВАМИ У БОЛЬНЫХ РЕВМАТОИДНЫМ АРТРИТОМ // Лікарська справа. 2009. № 3/4. С. 44–49.
  7. Гладких Ф. В., Степанюк Н.Г. СУЧАСНІ ШЛЯХИ ПОСЛАБЛЕННЯ УЛЬЦЕРОГЕННОСТІ НЕСТЕРОЇДНИХ ПРОТИЗАПАЛЬНИХ ЗАСОБІВ: ДОСЯГНЕННЯ, НЕВИРІШЕНІ ПИТАННЯ ТА ШЛЯХИ ОПТИМІЗАЦІЇ // Запорожский медицинский журнал. 2014. № 2. С. 82–86. URL: http://zmj.zsmu.edu.ua/article/view/25437/22932
  8. Giuliano C., Wilhelm S., Kale-Pradhan P. ARE PROTON PUMP INHIBITORS ASSOCIATED WITH THE DEVELOPMENT OF COMMUNITY-ACQUIRED PNEUMONIA? A META-ANALYSIS // Exp. Rev. Clin. Pharmacol. 2012. No. 5 (3). Р. 337–344. doi: 10.1586/ecp.12.20
  9. Drepper M.D., Spahr L., Frossard J.L. CLOPIDOGREL AND PROTON PUMP INHIBITORS – WHERE DO WE STAND IN 2012? // World J. Gastroenterol. 2012. No. 18 (18). Р. 2161–2171. doi: 10.3748/wjg.v18.i18.2161
  10. Bezabeh S., Mackey A.C, Kluetz P., Jappar D., Korvick J. ACCUMULATING EVIDENCE FOR A DRUGDRUG INTERACTION BETWEEN METHOTREXATE AND PROTON PUMP INHIBITORS // Oncologist. 2012. No. 17 (4). Р. 550–554. doi: 10.1634/theoncologist.2011-0431
  11. Goldstein J.L., Cryer B. GASTROINTESTINAL INJURY ASSOCIATED WITH NSAID USE: A CASE STUDY AND REVIEW OF RISK FACTORS AND PREVENTATIVE STRATEGIES // Drug, healthcare and patient safety. 2014. Vol. 7. P. 31–-41. doi: 10.2147/dhps.s71976
  12. Pellicano R. GASTROINTESTINAL DAMAGE BY NON-STEROIDAL ANTI-INFLAMMATORY DRUGS: UPDATED CLINICAL CONSIDERATIONS // Minerva Gastroenterol Dietol. 2014. No. 60 (4). Р. 255–261.
  13. Garg A., Shoeb A., Moodahadu Subramanya L., Sharma A., Gandhi A., Akku S. AMTOLMETIN: A REAPPRAISAL OF NSAID WITH GASTROPROTECTION // Hindawi Publishing Corporation. Arthritis. 2016. Vol. 2016. Article ID 7103705. Р. 1–5. doi: 10.1155/2016/7103705
  14. Holzer P. LOCAL EFFECTOR FUNCTIONS OF CAPSAICIN-SENSITIVE SENSORY NERVE ENDINGS: INVOLVEMENT OF TACHYKININS, CALCITONIN GENE-RELATED PEPTIDE AND OTHER NEUROPEPTIDES // Neuroscience. 1988. No. 24. Р. 739–768. doi: 10.1016/0306-4522(88)90064-4
  15. Holzer P. NEURAL EMERGENCY SYSTEM IN THE STOMACH // Gastroenterology. 1998. No. 114. Р. 823–839. doi: 10.1016/S0016-5085(98)70597-9
  16. Holzer P. TRANSIENT RECEPTOR POTENTIAL (TRP) CHANNELS AS DRUG TARGETS FOR DISEASES OF THE DIGESTIVE SYSTEM // Pharmacol. Ther. 2011. No. 131 (1). Р. 142–170. doi: 10.1016/j.pharmthera.2011.03.006
  17. Geppetti P., Trevisani M. ACTIVATION AND SENSITISATION OF THE VANILLOID RECEPTOR: ROLE IN GASTROINTESTINAL INFLAMMATION AND FUNCTION // British Journal of Pharmacology. 2004. No.141. Р. 1313–1320. doi: 10.1038/sj.bjp.0705768
  18. Berthoud H.R., Patterson L.M., Willing A.E., Mueller K., Neuhuber W.L. CAPSAICIN-RESISTANT VAGAL AFFERENT FIBERS IN THE RAT GASTROINTESTINAL TRACT: ANATOMICAL IDENTIFICATION AND FUNCTIONAL INTEGRITY // Brain Res. 1997. No. 746. Р. 195–206.
  19. Mozsik G. CAPSAICIN AS A NEW ORALLY APPLICABLE GASTROPROTECTIVE AND THERAPEUTIC DRUG ALONE OR IN COMBINATION IN HUMAN HEALTHY SUBJECTS AND IN PATIENTS // Prog. Drug. Res. 2014. No. 68. Р. 209–258. doi: 10.1007/978-3-0348-0828-6_9
  20. Osama A. Shaikh Omar, Hassan M. Bukhari, Naser A. ElSawy, Eslam A. Header EFFICACY OF CAPSICUM FRUTESCENS IN CURING THE PEPTIC ULCER // International Journal of Pure and Applied Sciences and Technology. 2013. No. 15 (1). Р. 43–54.
  21. Mozsik G., Omar M.E. Abdel-Salam, Koji Takeuchi. CAPSAICIN – SENSITIVE NEURAL AFFERENTATION AND THE GASTROINTESTINAL TRACT: FROM BENCH TO BEDSIDE. Publisher: InTech, Croatia, 2014. 320 p. doi: 10.5772/57289
  22. Katary M.A., Salahuddin А. GASTROPROTECTIVE EFFECT OF VANILLIN ON INDOMETHACININDUCED GASTRIC ULCER IN RATS: PROTECTIVE PATHWAYS AND ANTI-SECRETORY MECHANISM // Clin. Exp. Pharmacol. 2017. No. 7. Р. 232. doi: 10.4172/2161-1459.1000232
  23. Степанюк Н.Г., Томашевський А.В., Степанюк А.Г., Коваль В.С. ХАРАКТЕРИСТИКА ГАСТРОПРОТЕКТОРНОЇ ДІЇ КОРВІТИНУ НА МОДЕЛІ АСПІРИНОВОЇ ГАСТРОПАТІЇ // Теоретична і експериментальна медицина. 2006. № 1. С. 70–73.
  24. Pauls F.N., Wick A.N., MacKay E.M. AN ASSAY METHOD FOR ANTIULCER SUBSTANCES // Gastroenterology. 1947. No. 8. P. 774–782.
  25. Шварц Г.Я., Сюбаев Р. Д. Методологические рекомендации по доклиническому изучению нестероидных противовоспалительных лекарственных средств. Руководство по проведению доклинических исследований лекарственных средств. Часть первая. М.: Гриф и К., 2012. С. 746–758.
  26. Стальная И.Д., Гаришвили Т.Г. Метод определения малонового диальдегида с помощью тиобарбитуровой кислоты. Современные методы в биохимии. М.: Медицина, 1997. С. 66–68.
  27. Королюк М.А., Иванова Л.И., Майорова И.Г., Токарев В.Е. МЕТОД ОПРЕДЕЛЕНИЯ АКТИВНОСТИ КАТАЛАЗЫ // Лабораторное дело. 1988. № 1. С. 16–19.
  28. Левицький А.П., Почтар В.М., Макаренко О.А., Гридіна Л.І. АНТИОКСИДАНТНО-ПРООКСИДАНТНИЙ ІНДЕКС СИРОВАТКИ КРОВІ ЩУРІВ З ЕКСПЕРИМЕНТАЛЬНИМ СТОМАТИТОМ І ЙОГО КОРЕКЦІЯ ЗУБНИМ ЕЛІКСИРАМИ // Одеський медичний журнал. 2006. № 1. С. 22–25.
  29. Miranda K.M., Espey M.G., Wink D.A. A RAPID, SIMPLE SPECTROPHOTOMETRIC METHOD FOR SIMULTANEOUS DETECTION OF NITRATE AND NITRITE // Nitric Oxide. 2001. Vol. 5. No. 1. Р. 62–71. doi: 10.1006/niox.2000.0319
  30. Green L.C., Waqner D.A., Glogowski J., Skipper P.L., Wishnok J,S., Tannenbaum S.R. ANALYSIS OF NITRATE, NITRITE ANDNITRATE IN BIOLOGICAL FLUIDS // Analyt. Biochem. 1982. Vol. 126. Р. 131–138. doi: 10.1016/0003-2697(82)90118-X
  31. Zar J.H. Biostatistical analysis (5th ed.). Englewood Cliffs N.J.: Prentice-Hall, 2010. 751 р.
  32. Burdan F., Sek A., Burak B. LEVEL OF MALONDIALDEHYDE AFTER SHORT-TIME OMEPRAZOLE ADMINISTRATION // Med. Sci. Monit. 2001. Vol. 7. P. 89–92.
  33. Domotor A. Сapsaicin-sensitive afferentation and human gastrointestinal tract: Doctoral (Ph.D) Dissertation. Science of Pharmacology Doctoral School “Optimalisation of drug”; Pеcs, 2014. 66 р.
  34. Szabo I.L., Czimmer J., Mozsik G. CELLULAR ENERGETICAL ACTIONS OF “CHEMICAL” AND “SURGICAL” VAGOTOMY IN GASTROINTESTINAL MUCOSAL DAMAGE AND PROTECTION: SIMILARITIES, DIFFERENCES AND SIGNIFICANCE FOR BRAIN-GUT FUNCTION // Curr. Neuropharmacol. 2016. Vol. 14. No. 8. P. 901–913. doi: 10.2174/1570159X14666160719121725
  35. Барышникова Н.В., Белоусова Л.Н., Едемская М.А. НЕСТЕРОИДНЫЙ ПРОТИВОВОСПАЛИТЕЛЬНЫЙ ПРЕПАРАТ С ГАСТРОПРОТЕКТОРНЫМ ДЕЙСТВИЕМ – МИФ ИЛИ РЕАЛЬНОСТЬ? // Therapia. 2015. No. 7/8. С. 51–53.
  36. Qandil A.M. PRODRUGS OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS), MORE THAN MEETS THE EYE: A CRITICAL REVIEW // Int. J Mol Sci. 2012. No. 13. Р. 17244–17274. doi: 10.3390/ijms131217244
  37. Borhade N., Pathan A.R., Halder S., Karwa M., Dhiman M., Pamidiboina V., Gund M., Deshattiwar J.J., Mali S.V., Deshmukh N.J., Senthilkumar S.P., Gaikwad P., Tipparam S.G., Mudgal J., Dutta M.C., Burhan A.U., Thakre G., Sharma A., Deshpande S., Desai D.C., Dubash N.P., Jain A.K., Sharma S., Nemmani K.V., Satyam A. NO-NSAIDS. PART 3: NITRIC OXIDE-RELEASING PRODRUGS OF NON-STEROIDAL ANTIINFLAMMATORY DRUGS // Chem. Pharm. Bull. 2012. No. 60 (4). Р. 465–481. doi: 10.1248/cpb.60.465

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