Se-methylselenocysteine modulates antioxidant response of rat spleen to ionizing radiation

Whole body irradiation with a single 10-Gy dose caused increase in lipid peroxidation and a transient decrease in cellular glutathione content in rat spleen, demonstrating elevated oxidative stress. The irradiation also caused increases in activities of glutathione peroxidase (GPx), glutathione reductase (GR), and glucose 6-phosphate dehydrogenase (G6PD), the enzymes carrying out glutathione redox cycling; but not glutamate cysteine ligase (GCL), the enzyme in glutathione synthesis process. Increases in catalase (CAT) activity and heme oxygenase-1 (HO-1) and glutathione S-transferase pi (GSTpi) protein levels were also exhibited after irradiation. Administration of Se-methylselenocysteine (MSC) (0.75 mg/rat/day, for 1 week) resulted in increases in GPx, G6PD, and CAT activities and GSTpi protein level in non-irradiated spleen, without affecting glutathione and lipid peroxidation levels. The MSC pretreatment prior to irradiation abrogated the irradiation-induced increase in lipid peroxidation, and it induced increases in glutathione content, GCL, GPx and CAT activities, and HO-1, GSTpi, and peroxiredoxin 2 protein levels upon irradiation. Our results suggest a role for MSC pretreatment in prevention of irradiation-induced oxidative damage in spleen by reinforcing antioxidant capacity, particularly the glutathione system.