Inflammatory bowel disease (IBD) which includes ulcerative colitis (UC) is one of the most serious and currently unsolved problems in modern gastroenterology. In terms of severity and frequency of complications, IBD occupies the leading position among gastrointestinal tract diseases. The etiology of IBD is still not fully understood. It is probably of an autoimmune nature, and the main causes are considered to be hereditary predisposition, allergic reactions, nutrition, etc. Due to the fact that tumor growth is usually accompanied by inflammation of tumor nodules in adjacent apparently normal tissue and prolonged pharmaceutical suppression of inflammation significantly reduces the risk of tumor development, chronic UC is considered as a precursor condition for tumorigenesis. Moreover, the rate of colorectal cancer cases among people with UC history exceeding 10 years increases eightfold compared to the average population. Protein kinase inhibitor pyrrole derivatives 1-(4-Cl-benzyl)-3-Cl-4-(CF3-fenylamino)- 1Н-pyrrol-2,5-dione (MI-1) and 5-amino-4-(1,3-benzothiazole-2-yl)-1-(3-methoxyphenyl)- 1,2-dihydro-3H-pyrrole-3-one (D1) have been synthesized at the Chemistry Department of Taras Shevchenko National University of Kyiv. A complex study of biologically active pyrrole derivatives concerning their anti-inflammatory effects on colonic mucosa on the experimental ulcerative colitis model and possible mechanisms of their action has not been performed. Pyrrole derivatives can inhibit such protein kinases as Yes, Src(h), ZAP70, Syk(h), PDK1, EGFR, IGF-1R, VEGFR. These substances reveal antiproliferative and proapoptotic action toward malignant cells without significant effects on the proliferation and survival of normal cells.
Prednisolone was used as a reference anti-inflammatory drug of glucocorticoid nature. It was administered intraperitoneally at a dose of 0.7 mg/kg. The compounds were administered 2 h after the first administration of acetic acid. Total protein was estimated quantitatively, as described by Lowry et al., 1951. The content of malonic dialdehyde, protein carbonyl groups, and the activity of antioxidant enzymes as indicators of colon mucosa redox status were measured spectrophotometrically. Statistical analysis of the results was performed using MS Excel-2013.
The etiology of IBD is still not fully understood, the main causes are considered to be hereditary predisposition, allergic reactions, nutrition, etc. In this regard, it is important to prevent this pathology, in particular with the help of food supplements of natural origin, such as vegetable oils of flax and milk thistle, which are used in traditional medicine, including inflammatory diseases of the digestive system.
In case of chronic colitis, the number of carbonyl groups and lipid peroxidation products in the colonic mucosa is increased, indicating the development of oxidative stress. It has been found that at chronic colitis pyrrole derivatives reduce manifestations of inflammation and contribute to the restoration of the normal structure of the mucous membrane (comparative to prednisolone as a standard anti-inflammatory drug), which suggests their anti-inflammatory effectiveness. At the same time, an increase in total bilirubin under exposition to pyrrole derivatives may be a sign of adverse effects on the rats’ liver. It was shown that the use of linseed oil both cold and hot-pressed under conditions of adding it to the feed in an amount of 10% for 2 weeks prevents the development of inflammatory and destructive changes in the colon of rats with acute colitis and its negative consequences in the liver (for approaching to the normal values of serum markers of its functional activity). The data obtained may indicate that one of the mechanisms of implementation of the anti-inflammatory action of these substances is their ability to reduce oxidative stress - one of the main factors and promoters of inflammation.
