STATE OF THE GLUTATHIONE SYSTEM IN THE THYMUS OF WHITE RATS DURING THE INDUCTION OF COLORECTAL CARCINOGENESIS

Abstract

Introduction. Colorectal cancer (CRC) remains one of the most aggressive forms of neoplasia, characterized not only by local destruction of intestinal tissues but also by pronounced systemic metabolic disturbances. The progression of CRC is accompanied by an increase in markers of lipid peroxidation and depletion of the endogenous thiol pool in organs distant from the tumor. Of particular concern is the condition of immunocompetent organs, especially the thymus, which is the central organ of T-cell immunogenesis. The study aimed to investigate the state of the glutathione system in the thymus of white rats during the progression of experimental colorectal carcinogenesis. Methods. The study was performed on 98 white male outbred rats. The animals were divided into groups: I – intact animals; II – animals in which colorectal cancer was induced by injections of N,N-dimethylhydrazine hydrochloride. The induction period lasted 210 days, and the animals were euthanized every 30 days to monitor the dynamics of changes (7 study time points). The level of GSH in thymus homogenate was determined spectrophotometrically at a wavelength of 412 nm based on the intensity of the color of the thionitrophenyl anion formed by the reaction of free SH groups with Ellman’s reagent. GPx activity in thymus homogenate was determined spectrophotometrically at a wavelength of 340 nm by the rate of GSH oxidation in the presence of hydrogen peroxide and sodium azide. GR activity was measured spectrophotometrically at 340 nm by the rate of decrease in NADPH concentration consumed for the reduction of oxidized glutathione. Statistical analysis of the obtained results was performed using an independent two-sample two-tailed Student’s t-test and one-way analysis of variance (ANOVA) followed by Tukey’s post-hoc test. Results and discussion. In the thymus homogenate of intact rats, a gradual decrease in GSH level as well as GPx and GR activities was observed. Although these changes were mostly not statistically significant between consecutive time points, a significant decline relative to the baseline level was detected at the later stages of the experiment. Under conditions of N,N-dimethylhydrazine-induced carcinogenesis, early adaptive fluctuations in the activity of glutathione system components were observed, followed by their progressive suppression compared with intact values, reaching 30,38 % for GSH, 30,27 % for GPx, and 28,54 % for GR by day 210. Conclusions. The development of N,N-dimethylhydrazine-induced neoplastic process is accompanied by phase-dependent changes in the glutathione system in the thymus of white rats: at early stages, a slight increase in GSH level and GPx and GR activities is observed, reflecting a compensatory response, whereas at later stages their significant suppression occurs, indicating depletion of the antioxidant potential of the organ.