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ECPB 2019, 87(3): 30–36
https://doi.org/10.25040/ecpb2019.03.030
Research articles

Status of the Antioxidant System in Rats under the Conditions of Dimethylhydrazine-Induced Changesorogenesis and Application of Citostaitic Therapy

L.E. GRYTCISHIN, L. S. FIRA, P.H. LYKHATSKYI
Abstract

It is known that the development of the tumor is accompanied by a change in the oxidative- reducing equilibrium with the participation of active forms of oxygen. This leads to activation of free radical oxidation processes and violations in the functioning of the antioxidant system. A common method for treating malignant tumors is chemotherapy with cytostatic drugs, which, however, is not devoid of significant disadvantages. Experimental models of cancer are widely used to study carcinogenesis and the search for new antitumor drugs. One of them is the dimethylhydrazine model.

Objective. The aim of the study is to determine the patterns of changes in the antioxidant protection system parameters in the case of 1,2-dimethylhydrazine poisoning of rats and after application of cytostatics.

Materials and methods. In rats, the features of the development of cytological processes in conditions of induced colon cancer, caused by the administration of 1,2-dimethylhydrazine and after the use of Xeloda cytostatics, were investigated. 1,2-dimethylhydrazine was administered subcutaneously at a dose of 7.2 mg / 1 time per week for 30 weeks. Xeloda was administered intragastrically daily at a dose of 134 mg / kg of animal body weight for 21 days, starting immediately after a 7-month simulation of cancer process. For research, blood serum and liver homogenate were used. Blood serum and liver homogenate tested the content of TBC-active products and catalase activity; in serum, the content of ceruloplasmin and in the liver superoxide dismutase activity. All manipulations with experimental animals were carried out in compliance with the rules of the "European Convention for the Protection of Vertebrate Animals used for experimental and other scientific purposes".

Results. In conditions of induced oncogenesis in blood serum, a statistically significant increase in TBK-AP content was found, which significantly increased by 3.5 times in the 7th month of the experiment compared to a similar indicator of the control group of animals. A similar tendency to increase was observed in determining the content of TBK-AP in the liver homogenate in conditions induced by oncogenesis. The use of cytostatics Xeloda during 14 and 21 days did not lead to a decrease in the TBK-AP content, but on the contrary provoked an increase in this indicator in both serum and in the liver homogenate of the affected animals. The use of cytostatic therapy during 14 and 21 days led to an even greater decrease in SOD activity (in 1,4 and 1,5 times, respectively), compared with a group of animals with DMG-lesions. With DMG-induced carcinogenesis in blood serum of rats, the content of CP is significantly increased. Throughout the experiment, the serum of blood and liver of animals significantly decreased catalase activity. The use of the cytostatic for experimental animals with DMG-lesions has led to an even greater reduction of this indicator in serum and liver tissue.

Conclusions. In conditions of chemically induced carcinogenesis, violations of the state of antioxidant equilibrium were established due to accumulation of lipoperoxidation products, namely, TBC-reactive substances and reduction of antioxidant enzymes activity, in particular, superoxide dismutase and catalase. It has been established that the use of Xeloda cytostatic drug treatment results in even greater imbalance of the antioxidant system of white rats in the conditions of the simulated onco process, indicating the hepatotoxic effect of this agent and requires additional administration of hepatoprotective agents in the body.

Received: 17.09.2019

Keywords: dimethylhydrazine, adenocarcinoma of the colon, xeloda cytostatic, lipoperoxidation, antioxidant system

Full text: PDF (Ukr) 363K

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