PROCESSES OF LIPOPEROXIDATION AND RESPIRATION OF MITOCHONDRIA IN RAT LIVER UNDER THE ACTION OF THIAZOLES DERIVATIVES IN VITRO

Abstract

One of the main problems of chemotherapy is development of negative side effects, when anti-tumor drugs damage healthy cells, in particular hepatocytes. Liver is the main detoxifying organ in human and animals. This organ plays an important role in the excretion of drugs from the body. Changes in free radical oxidation processes and respiratory function of mitochondria in liver cells following the effects of newly synthesized antitumor agents may indicate adverse side effects that often occur after taking such substances. It was shown that thiazole derivatives passess anti-neoplastic activity against cancer cells in vitro. The influence in vitro of newly synthesized derivatives of thiazoles (N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide and 8-methyl-2-Me-7-[tri­fluoro­methyl-phenylmethyl]-pyrazolo-[4,3-e]-[1,3]-thiazolo-[3,2-a]-pyrimidin-4(2H)-one) in concentarion of 1, 10 and 50 mM on lipid peroxidation processes in hepatocyte membranes, respiration and oxidative phosphorylation in rat liver mitochondria was studied. The effects of these substances did not reveal changes in the products of the primary peroxide lipid oxidation, and the content of secondary products was significantly reduced. Such results may indicate that the studied substances might to interact with the active forms of Oxygen, while the antioxidant defense system was not changed. These results may also indirectly indicate that the thiazole derivatives not only do not activate, but also decrease the formation of peroxide oxidation products. The processes of respiration and oxidative phosphorylation in liver mitochondria practically did not change due to the influence of the studied thiazole derivatives. The only exceptions when energy changes were observed at using high doses (50 mM) of substances with nonselective effects. Since the studied thiazole derivatives, as shown earlier, exhibit high cytotoxicity to cancer cells, these substances can be applied as antitumor drugs with minimal negative side effects.