FREE-RADICAL PROCESSES IN NK/Ly LYMPHOMA CELLS AND HEPATOCYTES UNDER THE EFFECT OF THIAZOLE DERIVATIVE
About the author:
Shalai Ya. R., Mandzynets S. M., Hreniukh V. P., Finiuk N. S., Babsky A. M.
CLINICAL AND EXPERIMENTAL MEDICINE
Type of article:
Research purpose. To study the influence of new thiazole derivative N-(5-Benzyl-1,3-thiazole-2-yl)-3,5dimethyl-1-benzofuran-2-carboxamide on the level of primary and secondary products of peroxide lipid oxidation, and superoxide radicals in the mouse Nemeth-Kellner lymphoma (NK/Ly) cells and hepatocytes. Object and research methods. Studies were performed on nonlinear male mice weighing 20-30 g. Two groups of mice were used. Mice from the first group grafted lymphoma and healthy mice from the second group were used for study of liver. The ascites form of lymphoma was passaged by intraperitonial inoculation of 10-15 million cancer cells to mice. Thiasole derivative (compound 1) was dissolved in dimethyl sulfoxide and added to the test sample (lymphoma or liver homogenate) in final concentrations of 1, 10 and 50 μM. The levels of lipid hydroperoxides, positive products of thiobarbituric acid (TBA) and superoxide radical were determined spectrophotometrically in a homogenate of lymphoma cells and liver homogenate after incubation with the drug for 10 minutes. Research results and their discussion. In the homogenate of lymphoma, the level of hydroperoxides has increased significantly by compound 1, that may indicate a damaging in the antioxidant defense system, while the hepatocyte fraction in the membrane fraction has not changed. The level of TBA-positive products has not changed in both lymphoma homogenate and in the liver homogenate. The level of superoxide radical significantly reduced in lymphoma under the influence of compound 1. Thus, the derivative of thiazole activates the processes of the formation of primary products of peroxide oxidation of lipids in the cell-lymphoma cells. At the same time, there is a significant decrease in the level of superoxide radicals. Such changes in peroxide oxidation may increase the sensitivity of lymphoma cells to antitumor drugs. Conclusions 1. In lymphoma homogenate thiazole derivative increases the level of hydroperoxides, whereas the content of TBА-positive products does not change. At the same time, the level of superoxide radicals decreases, which may indicate that compound 1 may interact with the active forms of oxygen. 2. Unlike in lymphoma cells, the presence of compound 1 in the liver homogenate does not change the level of hydroperoxides and the content of TBА-positive products. The level of the superoxide radical was slightly reduced by the action of the compound 1 only at a concentration of 10 μM. 3. Thus, the studied thiazole derivative activates the processes of the formation of primary products of lipid peroxidation in lymphoma cells and practically does not affect these processes in the healthy liver. It can be assumed that the cytotoxic action of the thiazole derivative is realized through the interaction with active forms of Oxygen. Such changes in peroxide oxidation should increase the sensitivity of lymphoma cells to antitumor compounds.
lymphoma, thiazole derivatives, free radical processes, cytotoxicity
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Publication of the article:
«Bulletin of problems biology and medicine» Issue 1 Part 2 (143), 2018 year, 234-238 pages, index UDK 577.35+577.352