Influence of the 4-thiazolidinone derivative Les-6490 on the inflammatory process in rats compared to nimesulide

Abstract

Nonsteroidal anti-inflammatory drugs, which are used to treat numerous diseases, can cause a number of side effects. Therefore, the development of new molecules with anti-inflammatory and antimicrobial properties is an important task of modern medicine and veterinary medicine. A promising group of drugs with the above-described action are derivatives of 4-thiazolidinones. The thiazolidinone ring is a part of many existing potential antimicrobial and anti-inflammatory agents. The combination with a pharmacophore pyrazole moiety in the same structure, may result in enhanced therapeutic benefit. Aim. To assess the effects of the 4-thiazolidinone derivative Les-6490 and the conventional anti-inflammator y agent Nimesulide on hematological and biochemical parameters in rats within the context of an induced inflammatory process. Methods. The inflammatory process in animals was modeled with complete Freund’s adjuvant. (CFA). The assessment of changes in the animal body was carried out by the biochemical indicators of blood serum: activity of transaminases and alkaline phosphatase, indicators of total protein and albumin content, creatinine and urea levels, indicators of lipid metabolism (total cholesterol and triglycerides), quantitative levels of phosphorus and calcium as markers of mineral exchange. The results. The compound Les-6490 slows down the development of the inflammatory process in the AF inflammation model. It was determined that the development of the СFA-induced inflammatory process was not accompanied by significant changes in the concentration of total protein and albumin. Nimesulide caused a significant 22.7 % (p < 0.001) decrease in the albumin concentration, whereas no changes were observed with the compound Les-6490 against the background of FA. The self action of Les-6490 was accompanied by a significant decrease of urea compared to the control. The introduction of Les-6490 against the background of the inflammatory process led to a 9.9 % (P < 0.001) increase in the level of creatinine in the blood and a decrease in the activity of transaminases. It was confirmed that the action of Nimesulide is accompanied by a decrease in the amount of phosphorus and calcium in the serum, whereas Les-6490 does not show such effect. Conclusions. The studied compound Les-6490 is not inferior to the level of anti-inflammatory activity of Nimesulide in markers of the inflammatory process; the research of influence of the compound Les-6490 on the markers of liver diseases in comparison with the action of Nimesulide did not reveal a significant hepatotoxic effect of the substance; the compound Les-6490 showed a hypolipidemic effect that was similar to the effects of Nimesulide, both under the conditions of self-administration and when modeling the inflammatory process; the investigated compound can be considered promising for further research as a substance with an anti-inflammatory effect. The compound Les-6490 slows down the development of the inflammatory process in the AF inflammation model.