The Effects of Low-Dose-Rate γ-irradiation on Forced Swim Test-Induced Immobility and Oxidative Stress in Mice

The forced swim test (FST) induces immobility in mice. Low-dose (high-dose-rate) X-irradiation inhibits FSTinduced immobility in mice due to its antioxidative function. We evaluated the effects of low-dose γ-irradiation at a low-dose-rate on the FST-induced depletion of antioxidants in mouse organs. Mice received whole-body low-dose-rate (0.6 or 3.0 mGy/h) of low-dose γ-irradiation for 1 week, followed by daily FSTs (5 days). The immobility rate on day 2 compared to day 1 was significantly lower in the 3.0 mGy/h irradiated mice than in sham irradiated mice. The FST significantly decreased the catalase (CAT) activity and total glutathione (t-GSH) content in the brain and kidney, respectively. The superoxide dismutase (SOD) activity and t-GSH content in the liver of the 3.0 mGy/h irradiated mice were significantly lower than those of the non-FST-treated mice. The CAT activity in the lungs of mice exposed to 3.0 mGy/h γ-irradiation was higher than that of non-FST treated mice and mice treated with FST. However, no significant differences were observed in the levels of these antioxidant markers between the sham and irradiated groups except for the CAT activity in lungs. These findings suggest that the effects of low-dose-rate and low-dose γ-irradiation on FST are highly organ-dependent

X-Irradiation at 0.5 Gy after the forced swim test reduces forced swimming-induced immobility in mice

The forced swim test (FST) is a screening model for antidepressant activity; it causes immobility and induces oxidative stress. We previously reported that radon inhalation has antidepressant-like effects in mice potentially through the activation of antioxidative functions upon radon inhalation. This study aimed to investigate the effect of prior and post low-dose X-irradiation (0.1, 0.5, 1.0 and 2.0 Gy) on FST-induced immobility and oxidative stress in the mouse brain, and the differences, if any, between the two. Mice received X-irradiation before or after the FST repeatedly for 5 days. In the post-FST-irradiated group, an additional FST was conducted 4h after the last irradiation. Consequently, animals receiving prior X-irradiation (0.1 Gy) had better mobility outcomes than sham-irradiated mice; however, their levels of lipid peroxide (LPO), an oxidative stress marker, remained unchanged. However, animals that received post-FST X-irradiation (0.5 Gy) had better mobility outcomes and their LPO levels were significantly lower than those of the sham-irradiated mice. The present results indicate that 0.5 Gy X-irradiation after FST inhibits FST-induced immobility and oxidative stress in mice

Evaluation of the redox state in mouse organs following radon inhalation

Radon inhalation activates antioxidative functions in mouse organs, thereby contributing to inhibition of oxidative stress-induced damage. However, the specific redox state of each organ after radon inhalation has not been reported. Therefore, in this study, we evaluated the redox state of various organs in mice following radon inhalation at concentrations of 2 or 20 kBq/m(3) for 1, 3 or 10 days. Scatter plots were used to evaluate the relationship between antioxidative function and oxidative stress by principal component analysis (PCA) of data from control mice subjected to sham inhalation. The results of principal component (PC) 1 showed that the liver and kidney had high antioxidant capacity; the results of PC2 showed that the brain, pancreas and stomach had low antioxidant capacities and low lipid peroxide (LPO) content, whereas the lungs, heart, small intestine and large intestine had high LPO content but low antioxidant capacities. Furthermore, using the PCA of each obtained cluster, we observed altered correlation coefficients related to glutathione, hydrogen peroxide and LPO for all groups following radon inhalation. Correlation coefficients related to superoxide dismutase in organs with a low antioxidant capacity were also changed. These findings suggested that radon inhalation could alter the redox state in organs; however, its characteristics were dependent on the total antioxidant capacity of the organs as well as the radon concentration and inhalation time. The insights obtained from this study could be useful for developing therapeutic strategies targeting individual organs

Radon inhalation decreases DNA damage induced by oxidative stress in mouse organs via the activation of antioxidative functions

Radon inhalation decreases the level of lipid peroxide (LPO); this is attributed to the activation of antioxidative functions. This activation contributes to the beneficial effects of radon therapy, but there are no studies on the risks of radon therapy, such as DNA damage. We evaluated the effect of radon inhalation on DNA damage caused by oxidative stress and explored the underlying mechanisms. Mice were exposed to radon inhalation at concentrations of 2 or 20 kBq/m(3) (for one, three, or 10 days). The 8-hydroxy-2 '-deoxyguanosine (8-OHdG) levels decreased in the brains of mice that inhaled 20 kBq/m(3) radon for three days and in the kidneys of mice that inhaled 2 or 20 kBq/m(3) radon for one, three or 10 days. The 8-OHdG levels in the small intestine decreased by approximately 20-40% (2 kBq/m(3) for three days or 20 kBq/m(3) for one, three or 10 days), but there were no significant differences in the 8-OHdG levels between mice that inhaled a sham treatment and those that inhaled radon. There was no significant change in the levels of 8-oxoguanine DNA glycosylase, which plays an important role in DNA repair. However, the level of Mn-superoxide dismutase (SOD) increased by 15-60% and 15-45% in the small intestine and kidney, respectively, following radon inhalation. These results suggest that Mn-SOD probably plays an important role in the inhibition of oxidative DNA damage