Radioprotective effects of N-acetylcysteine on rats' brainstem following megavoltage X-irradiations.

PURPOSE: This study aimed to determine the radioprotective effect of N-acetylcysteine (NAC) on the radiation-induced oxidative stress (OS) in the rats' brainstem. MATERIALS AND METHODS: Eighty rats in four identical groups, including vehicle control (VC), irradiation alone (RAD), irradiation with 1 g/kg of NAC treatment (RAN), and NAC treatment without radiation (NAC) were used. Whole-brain irradiation was performed with a single dose of 25 Gy. The rats received the treatments via intraperitoneal (IP) injection 1 h before the irradiation process. Nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC), and glutathione peroxidase (GPx) were measured in the rats' brainstem and compared between the groups. Furthermore, the pathological study was performed to assess tissue damage after 24 h, 72 h, and 5 days of irradiation. RESULTS: The levels of NO and MDA in the brainstem tissue for the RAD group were 60.37 ± 3.35 µmol/L and 45.10 ± 2.48 µM, respectively, which were higher than those of VC group (NO: 30.41 ± 1.83 µmol/L; MDA: 31.02 ± 1.71 µM). The level of SOD, CAT, TAC, and GPx declined in the RAD compared to the VC group. Pre-treatment with NAC decreased the level of NO and MDA and also enhanced the antioxidant activities. The greatest pathological changes in the rats' brainstems were seen in RAD animals compared to the VC group at 24 h, 72 h, and 5 days. Furthermore, the pathological changes were not observed in the NAC group in all the assessed times. CONCLUSION: Based on the results, NAC can decrease the irradiation-induced oxidative stress and pathology damages in the rats' brainstem. It can be concluded that NAC can be an appropriate radioprotection candidate for the human brainstem.

Neuroprotective effect of melatonin on radiation-induced oxidative stress and apoptosis in the brainstem of rats.

This study aimed to determine the effects of melatonin on irradiation-induced apoptosis and oxidative stress in the brainstem region of Wistar rats. Therefore, the animals underwent whole-brain X-radiation with a single dose of 25 Gy in the presence or absence of melatonin pretreatment at a concentration of 100 mg/kg BW. The rats were allocated into four groups (10 rats in each group): namely, vehicle control (VC), 100 mg/kg of melatonin alone (MLT), irradiation-only (RAD), and irradiation plus 100 mg/kg of melatonin (RAM). An hour before irradiation, the animals received intraperitoneal (IP) melatonin and then were killed after 6 hr, followed by measurement of nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and total antioxidant capacity (TAC) in the brainstem region. Furthermore, the western blot analysis technique was performed to assess the caspase-3 expression level. Results showed significantly higher MDA and NO levels in the brainstem tissues for the RAD group when compared with the VC group (p < .001). Moreover, the irradiated rats exhibited a significant decrease in the levels of CAT, SOD, GPx, and TAC (p < .01, p < .001, p < .001, and p < .001, respectively) in comparison to the VC group. The results of apoptosis assessment revealed that the expression level of caspase-3 significantly rose in the RAD group in comparison with the VC group (p < .001). Pretreatment with melatonin ameliorated the radiation-induced adverse effects by decreasing the MDA and NO levels (p < .001) and increasing the antioxidant enzyme activities (p < .001). Consequently, the caspase-3 protein expression level in the RAM group showed a significant reduction in comparison with the RAD group (p < .001). In conclusion, melatonin approximately showed a capacity for neuroprotective activity in managing irradiation-induced oxidative stress and apoptosis in the brainstem of rats; however, the use of melatonin as a neuroprotective agent in humans requires further study, particularly clinical trials.