LEVEL OF REDUCED GLUTATHIONE IN COLORECTAL CANCER UNDER THE INFLUENCE OF 5-FLUOROURACIL AND MOLECULAR HYDROGEN
DOI:
https://doi.org/10.11603/mcch.2410-681X.2024.i3.14913Keywords:
colorectal cancer, molecular hydrogen, hydrogen water, reduced glutathioneAbstract
Introduction. Reduced glutathione plays a crucial role in maintaining cellular homeostasis and redox balance, serving as a key element of intracellular defense against reactive oxygen species. A decrease in its levels below a critical threshold is considered a marker of oxidative stress, which underlies the pathophysiology of various degenerative diseases, including carcinogenesis. However, there are conflicting results regarding the interaction between chemotherapy xenobiotics and reduced glutathione. The presence of oxidative stress in colorectal cancer necessitates effective antioxidant therapy, and it has been proven that molecular hydrogen exhibits potent antioxidant activity.
The aim of the study – to investigate the effect of molecular hydrogen-enriched water and 5-fluorouracil on the content of reduced glutathione in the blood serum of Wistar rats with colorectal cancer.
Research Methods. The experiments were conducted on 70 male Wistar rats. Colorectal cancer (CRC) was induced in the animals by subcutaneous administration of 1,2-dimethylhydrazine (DMH) at a dose of 7.2 mg/kg of body weight once a week for 30 weeks. 5-fluorouracil was administered intraperitoneally for 4 days at a dose of 12 mg/kg and then every other day for an additional 4 days at a dose of 6 mg/kg. The animals consumed molecular hydrogen-enriched water at a concentration of 0.6 ppm ad libitum. Euthanasia was performed under thiopental anesthesia. Blood serum was used for the analysis, and the content of reduced glutathione was determined by a colorimetric method. Statistical data analysis was performed using SPSS-22 software.
Results and Discussion. It was found that the content of reduced glutathione in the blood serum of rats that consumed tap water for 30 weeks during the modeling of CRC and molecular hydrogen-enriched water for only 30 days after CRC modeling was 10% higher than in rats with CRC that did not consume hydrogen water. In the blood serum of rats with colorectal cancer treated with 5-fluorouracil, the reduced glutathione level at the end of the experiment was 0.85 mmol/g of protein, which is 32 % lower than in the control group and 22 % lower than in the group that consumed hydrogen water for 30 days after CRC modeling. The reduced glutathione content in the serum of rats with colorectal cancer treated with 5-FU and who consumed molecular hydrogen-enriched water for 30 days after CRC modeling was 1.02 mmol/g of protein, which was 10 % higher (P≤0.05) than in the CRC group and 17 % higher than in the group treated with 5-FU that did not consume hydrogen water.
Conclusion. Modeling colorectal cancer and administering 5-fluorouracil in rats led to a reduction in the level of reduced glutathione in their blood serum. However, the consumption of molecular hydrogen-enriched water significantly increased the content of this antioxidant.
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