Effect of pyrrole derivatives on manifestations of inflammation in rats with chronic ulcerative colitis under prednisolone treatment

Abstract

Background. Previously, we have detected the antitumor and anti-inflammatory activities of pyrrole-derived protein kinase inhibitors - MI-1 (1-(4-Cl-benzyl)-3-Cl-4-(CF3-phenylamino) -1H-pyrrole-2,5-dione 1) and D1 (5-amino-4-(1,3-benzothiazole-2-yl)-1-(3-methoxyphenyl)-1,2-dihydro-3H-pyrrole-3-one) using rat colon cancer model. Therefore, pyrrole derivatives was aimed at detecting the anti-inflammatory effect on the model of ulcerative colitis caused by acetic acid in rats. Materials and Methods. 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 in 2 h after the first administration of acetic acid. Total protein was estimated quantitatively, as described by Lowry et al., 1951. Content of the 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. Results and Discussion. In case of chronic colitis, the number of carbonyl groups and lipid peroxidation products in the colonic mucosa are increased, indicating the development of oxidative stress. The injection of pyrrole derivatives separately contributes to the approaching these indicators to normal. Adding prednisolone does not have this effect. Colitis has been shown to have a decrease in superoxide dismutase activity, which is a typical phenomenon for chronic inflammation and may indicate depletion of the enzyme. In case of colitis, alanine aminotransferase activity and the content of direct bilirubin are increased, which indicates a liver injury and are systemic manifestations of inflammation of the colon. Pyrrole derivatives help to reduce the liver injury, which indicates the restoration of normal alanine aminotransferase activity and direct bilirubin content. Conclusion. It has been found that at chronic colitis pyrrole derivatives reduce the manifestations of inflammation, contribute to the normal structure of the mucous membrane (comparative to prednisolone as a standard anti-inflammatory drug). It suggests their anti-inflammatory effectiveness, while an increase in total bilirubin under exposition to pyrrole derivatives may be a sign of the adverse effects on the rat’s liver.