Influence of glutathione levels and activity of glutathione-related enzymes in the brains of tumor-bearing mice.

Oxidative stress takes place due to an imbalance between the production of reactive oxygen species (ROS) and the protection provided by cellular antioxidants. High levels of ROS are caused by tumor cells during tumor progression and may affect the functions of other important organs. The present study sought to investigate whether non-primary brain tumors affect reduced glutathione (GSH) levels and the activity of related enzymes in the brain. GSH contents, the activity of glutathione peroxidase (GPx), glutathione-s-transferase (GST), glutathione reductase (GR) as well as glutamate cysteine ligase (GCL) were determined in the brains of normal and tumor-bearing mice treated with the chemotherapy drug 5-Fluorouracil (5-Fu) or not. The results in S180 and H22 tumor-bearing mice showed that GSH levels and the activity of GPx, GST, and GCL all decreased while GR activity markedly increased in the brains of tumor-bearing mice compared to those of normal mice. Further investigation found that 5-Fu, a typical chemotherapy drug, significantly inhibited tumor growth but did not improve the loss of redox homeostasis in the brain caused by non-primary brain tumors. Overall, these results suggest that non-primary brain tumors can induce an ROS burden in the brain that cannot be reversed by the chemotherapy drug 5-Fu.