In recent years there has been a fairly high level of digestive system precancerous, which tends to increase. This remains a topical issue in modern medicine. Often one of the causes of cancer is impaired tyrosine kinase activation processes, which regulate different stages of growth and proliferation of cells. Therefore, a promising trend in modern medicine is associated with targeted highly selective medicinal products, in particular membrane tyrosine kinase inhibitors characterized by high antitumor, anti-inflammatory activity and lower toxicity as compared with traditional cytostatics. Medicinal products in this class include maleimidepyrrole derivative (MI-1) іn silico synthesized at Research and Production Biochemical Center of Taras Shevchenko National University. These products are targeted inhibitors of protein kinase, which due to the spatial structure of the molecule interacts with the ATP-binding centre of tyrosine protein kinases and is their effective blocker. Since the cytotoxic effect of the medicinal product MI-1 has been demonstrated on the transformed line and cancer cells, it is said to be a potential compound for using in clinical practice. The aim of the study was to evaluate the effect of the combination of prednisolone + MI-1 on the caecum mucosa on rats with ulcerative colitis. The studies were conducted on white mongrel male rats. The rats were housed under standard environmental conditions (23±1°C, 55±5 % humidity and a 12-h light: 12-h dark cycle) and maintained with free access to water and a standard laboratory diet ad libitum. The study was conducted in accordance with the generally accepted bioethical standards of humane treatment of laboratory animals, in accordance with national and international regulations on carrying out experimental tests (“European Convention for the Protection of Vertebrate Animals used for experimental and other scientific purposes” (Strasbourg, 1986), “General Ethical Principles of Animal Experiments”, adopted by the First National Congress on Bioethics (Kyiv, 2001). The model of ulcerative colitis was reproduced by 2-fold rectal administration of 1 ml of a 4% solution of acetic acid at intervals of one week. MI-1 at a dose of 2.7 mg/ kg was injected dissolved in sunflower oil containing 15% DMSO (0.1 ml in total) per os. Prednisolone (PJSC "BIOFARMA", Ukraine, solution for injection) at a dose of 0.7 mg/ kg was injected intraperitoneally in dilute physiological saline solution. Control animals received oil containing 15 % DMSO (0.1 ml in total). The obtained data indicate that under the conditions of exposure to prednisolone + MI-1 in the background of ulcerative colitis, intestinal damage is observed in females at the macroscopic level, whereas in males they were absent. On the micro level, in comparison with the colitis group, there was a suppressed inflammation in the rats of both sexes. Comparing the combination of prednisolone + MI-1 between both sexes, there is a decrease in the inflammatory process of males, which indicates a greater tendency of females to inflammatory bowel disease and lower sensitivity to anti-inflammatory therapy. Thus, the combination of prednisolone + MI-1 suppresses inflammation and promotes the restoration of the intestinal mucosa, that is, it exhibits anti-inflammatory and protective effects.
Keywords: ulcerative colitis, prednisolone, maleimadepyrrole derivative, intestinal mucosa
Full text: PDF (Ukr) 186K