INFLUENCE OF LONG-TERM ADMINISTRATION OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS ON THE LEVEL OF WHOLE GENOME DNA METHYLATION AND ITS FRAGMENTATION IN RATS

Burlakа K. A

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Epigenetics is the branch of genetics concerned with the study of inherited changes in the activity or function of genes that are not associated with any change in the DNA sequence itself. Although almost all cells of the body contain the same genetic information, not all genes are expressing simultaneously in all cell types. More broadly, epigenetic mechanisms mediate different gene expression patterns in different cells and tissues of multicellular organisms. In recent years, there has been a rapid growth in epigenetic research associated with the development of new molecular and cytological approaches. However, the main fundamental observations are connecting with the study of the processes of differentiation in development. Recent studies have found that chemical compounds can have an epigenetic effect, that is, affect the activity of the expression of certain genes. And most often this is due to people who have chronic diseases, because they are forced to use drugs for a long time, in order to improve the quality of life. It is known that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) leads to the formation of erosions, ulcers and oncological diseases of the stomach and intestines. It has been suggested that side effects are not only the result of mucosal damage under the influence of NSAIDs, but also the possible effect of NSAIDs on genes that regulate the cell cycle, especially with their long-term use. In the studies, 60 male rats were used, which were divided into four groups of 15 animals, which were administered daily for 3 months with NSAIDs: 1st – control (CG), sodium chloride solution 0.9%, 2nd – rats , which were injected with indomethacin, the 3rd group – rats that were injected with acetylsalicylic acid and the 4th group – rats that were injected with meloxicam. Long-term administration of all NSAIDs led to a statistically probable increase in whole-genome DNA methylation and intensification of its fragmentation processes. It is important to note that according to the degree of epigenetic impact, the effect of the studied NSAIDs was of varying severity. Indomethacin had the most pronounced effects (an increase in MspI/HpaII by 99%; DNA fragmentation by 90% relative to intact). Considering the established effects of NSAIDs, in terms of their ability to increase the level of genome-wide DNA methylation and their fragmentation, a promising direction is to study the level of methylation of genes that regulate the cell cycle of the stomach and intestines, as well as to study their expressive/biloxinsynthesizing function.

DNA methylation,epigenetics,ulcerogenic effect,non-steroidal anti-inflammatory drugs

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«Bulletin of problems biology and medicine» Issue 1 (168), 2023 year, 114-119 pages, index UDK 615.212.03:577.21-074/-076-092.9

10.29254/2077-4214-2023-1-168-114-119