Lynchak O. The influence of the maleimide derivative on the condition of the normal rat liver and bowel and with chemical-inducted carcinogenesis of the colon

Subject: liver, small and large bowel, blood, urine of rats under the influence of MI-1 and DMH, and MI-1 action on the background of DMH-induced colon carcinogenesis. Objective: To examine the influence of the maleimide derivative on the state of the gastrointestinal tract of intact animals and with chemically induced colon carcinogenesis, to study of the effectiveness of the maleimide derivative in the prevention of the development of DMH-induced colon cancer. Methods: A histological study of liver, small and large bowel, morphometric analysis, analysis of the development of colon tumors, counting their number and area, biochemical methods, statistical analysis. Results: MI-1 does not cause destructive changes in the liver and bowel. DMH action results in significant morphological and functional changes in liver metabolism that stipulates active carcinogens. After 6 weeks after withdrawal of DMH in the liver there are processes of recovery. In colon DMH action not only results in tumor development, but also affects on the mucosa. Depending on dose and duration of the introduction MI-1 partially or completely prevents the changes caused by DMH in the liver and bowel. MI-1 reduces the number and total area of colon cancer caused by DMH. The greatest efficiency of MI-1 demonstrated in the rectum. Also MI-1prevents oxidative DNA damage and the development of oxidative stress in rat liver which were caused by DMH. Novelty: For the first time it was investigated the morpho-functional state of liver, small and large intestine of rats after short-term (5 weeks) and long (20 and 26 weeks) effects of potential new antitumor drug maleimide derivative MI-1 - protein kinase inhibitor. We describe the morpho-functional state of liver, small intestine and received additional information on colon histology on the development of 1,2-dimethylhydrazine-induced colorectal cancer in rats. It is established the partial protective effect of MI-1 on the development of DMH-induced colon tumors in rats, and also the recovery of morpho-functional state of liver and bowel of rats with use of MI-1 on the background of the DMH carcinogenic. It was shown that MI-1 reduces oxidative DNA modifications, increased by DMH-induced tumorogenesis. Area use: Research is the foundation for further search and development of new anticancer drugs with target action. Histological changes that were found in segments of colon tissue, not affected by tumor growth ("conditionally healthy" tissue) in the development of chemically-induced carcinogenesis, can be used for diagnostic purposes. Results of the thesis are introduced into the educational process Biological Faculty of Kiev National Taras Shevchenko University.