Development of the inflammatory process and endogenic intoxication in colorectal cancer after the application of cytostatics and hepatoprotectors

Abstract

Background: Considerable attention is currently drawn to inflammation as one of the main risk factors in the development of colon cancer. The aggravation of endogenous intoxication under conditions of the oncological process is observed concurrently with the development of inflammatory processes in the body. [19]. The objective need for cytostatic therapy occurs under the development of colorectal cancer to inhibit tumor growth. It has been substantiated that cytostatic therapy can cause almost all known forms of hepatic diseases, which leads to the necessitate use of adjunct medication to eliminate the adverse effects of the cytostatics.

Material and methods: The experimental studies were conducted on white rats kept on a standard diet in the vivarium conditions. All procedures were performed in compliance with the regulations of «The European Convention for the protection of vertebrate animals used for experimental and other scientific purposes». The carcinogen 1,2-dimethylhydrazine.(DMH) was injected subcutaneously in the interscapular region at a dose of 7,2 mg/kg of body weight once a week for 30 weeks. The medication Xeloda was daily administered by an intragastric route at a dose of 134 mg/kg of animal’s body weight for 21 days, starting immediately after 7-month modeling of the oncological process. The hepatoprotector Glutargin was administered to eliminate adverse effects of thecytostatic upon the liver at a dose of 130 mg / kg for 21 days after modeling the oncological process and effect of the cytostatic agent Xeloda. Levels of pro- and anti-inflammatory interleukins in blood serum were determined by immunoenzyme technique. The endogenous intoxication level was measured through the accumulation of middle molecules in the blood serum.

Results and Discussion: It was established that the concentration of markers of endogenous intoxication in the blood serum - middle molecules of both fractions (with the predominance of branched-chain and aromatic amino acids) increased within seven months of dimethylhydrazine administration, reaching the peak concentration over the last month of the conducted experiment (the increase was 2.9 and 2, 8 times, respectively). The augmented concentration of pro-inflammatory IL-6 (by 3,6 times), as well the decreased concentration of anti-inflammatory IL-4 (by 50%) were determined within the same experimental period, indicating the development of inflammatory processes under conditions of colon cancer in rats. The cytostatic agent Xeloda, administered for 21 days, exacerbated the revealed disorders after the adenocarcinoma modeling. An even greater increase in the content of middle molecules, as well as the imbalance in the levels of cytokines, were observed after the administration of cytostatic. The level of pro-inflammatory cytokine was exaggerated by 28% compared to the experimental group of animals with dimethylhydrazine-induced carcinogenesis for 7 months. The hepatoprotector Glutargin, administered to eliminate adverse effects of the cytostatic, evidenced its efficacy under these conditions. The use of the hepatoprotector caused the decrease in the concentration of IL-6 by 1,7 times compared to the animals with induced adenocarcinoma administered the medication Xeloda, which indicates the inhibition of inflammatory processes under the pathological process.

Conclusions: It has been evidenced that administration of the hepatoprotector Glutargin leads to the normalization of the studied parameters in rats with induced carcinogenesis that were administered the cytostatic agent Xeloda, indicating the prospects of further research of its effect on inflammatory processes and indicators of endogenous intoxication in the dynamics of colorectal cancer development.