Models for studying gastro- and enteroprotective action of pharmaceuticals
The study of gastroprotective action of PA includes the following analyses:
the study of antiulcer action of PA in the model of stomach pyloric ligation by Shay method;
analysis of antiulcer activity of PA in the model of indomethacin-induced ulcer in rats;
an assessment of cytostatic action of PA against Helicobacter pylori;
the study of spasmolytic effect of PA ex vivo (an assessment of terminal ileum segment tonus) and in vivo (an assessment of intestinal transit in rats).
Assessment of PA activity in the model of an experimental pancreatitis in rabbits;
Study of PA effect on normalization of bile composition in the model of lithogenic diet.
Biochemical tests:
analysis of enzyme activity;
analysis of bile composition.
Assessment of gastric mucosal homogenate:
analysis of cytokine content;
analysis of enzyme activity.
Study of the effect of drugs in Helicobacter pylori
Morphological examination of gastric mucosa of each animal in the experiment accompanied by calculating the number of ulcerations in gastric mucosa (large, average and dot) and the percentage of animals with ulcers. Pauls index and ulcerogenesis index are calculated.
To assess the expressiveness of the reaction of rats to stressful influence, which Shay method of stomach ulcer induction is itself (surgery, twenty-hour pylorus ligation), it is possible to use the value of adrenal masses and the 11-oxycorticosteroid (11-OCS) concentration value in rat plasma.
Publications by topic:
Makarov V.G., Makarova M.N., Alexandrova A.E., Ryzhenkov V.E. The role of antioxidant system in gastroprotective action of camomille (Matricaria recutita L.) oil extract in stress-induced stomach mucous ulceration // Психофармакология и биологическая наркология. 2-3. 706-707.
Makarov V.G., Makarova M.N., Rydlovskaya A.V., Tesakova S.V., Zhorina A.S. Experimental assessment of function of metabolomic complexes // Phytopharm. 2008. 12 th International congress. Book of Leiden. Netherlands. 1-4 July 2008. P.70.
Makarov V.G., Shikov A.N., Pozharitskaya O.N., Kvetnaya A.S. Study of antibacterial activity of chamomile oil extract to Helicobacter pylori // Abstr. 50 fh Annual Congress “Society for Medicinal Plant Research”, Barcelona, 8-12 Sept. 2001, Barcelona, 2002. – A044. – P. 104.
Makarova M.N., Alexandrova A.E., Makarov V.G., Dadali V.A. The effect of camomile oil extract on the antioxidant system in experimentally induced stomach mucous ulceration // GA. Book of abstracts. Fascination facts future. August 31 – September 4. -2003. -Kiel, Germany. -P. 158.
Александрова А.Е., Кветная А.С., Дмитриева О.Л., Бащук С.В., Куренкова Т.Ю., Макарова М.Н., Рыженков В.Е. Антиульцирогенная активность нового препарата Гастроромазол на основе экстракта цветков ромашки аптечной // Актуальные проблемы создания новых лекарственных препаратов природного происхождения: Матер. VI международного съезда. –СПб. –2002. –С. 338-344.
Александрова А.Е., Макарова М.Н., Макаров В.Г., Куренкова Т.Ю. Действие Гастроромазола на перекисное окисление липидов и антиоксидантный статус в условиях экспериментального язвообразования // Актуальные проблемы создания новых лекарственных препаратов природного происхождения: Матер. VI международного съезда. –СПб. –2002. –С. 344-349.
Дадали В.А., Макаров В.Г. К вопросу эндоэкологического действия биологически активных соединений лекарственных и пищевых растений // V Междун. съезд “Актуальные проблемы создания новых лекарственных препаратов природного происхождения”, Санкт-Петербург – Петродворец, 5-7 июля 2001 г. Матер., СПб., 2001. – С. 387-396.
Макаров В.Г., Лифляндский В.Г., Лобанков О.В. и др. Экспериментально-клиническое изучение гастропротекторного и холеретического эффектов фитопрепарата “Эликсир Демидовский”. // Журн. Вопросы биол. мед. и фармацевтич. химии, М. – 1998. – N 2. – С. 38-41.
Макаров В.Г., Макарова М.Н., Рыдловская А.В., Тесакова С.В. Нутриметаболомика с позиций системной оценки функционирования метаболических комплексов // Вопросы питания. 2007. 76(3). 4-10.
Пахомова И.Н., Макарова М.Н., Егошина В.А. НПВП-индуцированные поражения желудочно-кишечного тракта по данным эксперимента // Гастроэнетрология Санкт-Петербурга. – 2013, № 3.
Прошин С.Н., Макаров В.Г., Макарова М.Н., Крышень К.Л., Ковшин А.В., Самусенко И.А. Ульцерогенное действие нестероидных противовоспалительных средств и гепатотоксичность нимесулида в эксперименте на крысах // Обзоры по клин. фармакол. и лек. терапии. 2012. 10(1). 28–34.
Фоминых Ю.А., Успенский Ю.П., Макарова М.Н., Макаров В.Г., Карачинская И.В. Исследование моторики кишечника мышей под действием стрессорных факторов //Российский журнал гастроэнтерологии, гепатологии, колопроктологии. -2011. -Т. XXI, №5. –С. 141. Приложение № 38. Материалы 17-й Российской гастроэнтерологической недели 10-12 октября 2011 г., г. Москва.
Kuksgauz I.A., Shekunova E.V., Kashkin V.A., Faustova N.M., Guschin Ya.A., Makarova M.N., Makarov V.G. Gastroprotective effect of Alfl utop on diclofenac-induced gastropathy in rats. Experimental and Clinical Gastroenterology. – 2019. – Vol. 166(№5). Р. 15-21. SUMMARY. The aim of the study was to evaluate the gastroprotective effect of Alflutop solution for injection (K. O. Biotechnos S. A., Romania) on gastropathy induced by diclofenac in rats. Materials and methods: rats were treated with Alflutop (intramuscularly) and diclofenac (intragastrically) for 20 consecutive days. The levels of prostaglandins (PG) were estimated in stomach tissue homogenate supernatant using 4 groups, for the pathological study – 2 groups. Results: diclofenac administration resulted in development of lesions of the gastric mucosa. The 30% of animals treated with diclofenac and Alflutop did not demonstrate any pathological abnormalities, whereas pathological changes were observed in 100% of animals treated with diclofenac only. The decrease in the frequency and severity of desquamation of the epithelium was detected in the animals treated with Alflutop and diclofenac compared with the diclofenac group. Measurement of PG in stomach tissue homogenates showed that diclofenac induced decrease of the PGE2, PGF2α and PGI metabolite – 6-keto-PGF1α. After discontinuation of diclofenac, PG levels continued to decline. The decrease of PGF2α and 6-keto-PGF1α was most pronounced (up to 16 and 20 times). Alflutop treatment was found to normalize the gastric levels of PGE2 and 6-keto-PGF1α by the 41th day of the experiment. Reduced by diclofenac PGF2α level was reinstated in the Alflutop group on the 21th day, on the 41th day PGF2α concentration exceeded the levels of the control group. Conclusion: thus, Alflutop therapy resulted in rapid recovery of PG synthesis which had been suppressed by diclofenac. The potential mechanisms of Alflutop gastroprotective effects are discussed [Full text is available in Russian].