Neuroprotective effects of alpha-lipoic acid on radiation-induced brainstem injury in rats.

Background and purpose: Alpha-lipoic acid (ALA) is an antioxidant with radioprotective properties. We designed the current work to assess the neuroprotective function of ALA in the presence of oxidative stress induced by radiation in the brainstem of rats. Experimental approach: Whole-brain radiations (X-rays) was given at a single dose of 25 Gy with or without pretreatment with ALA (200 mg/kg BW). Eighty rats were categorized into four groups: vehicle control (VC), ALA, radiation-only (RAD), and radiation + ALA (RAL). The rats were given ALA intraperitoneally 1 h before radiation and killed following 6 h, thereafter superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and total antioxidant capacity (TAC) in the brainstem were measured. Furthermore, a pathological examination was carried out after 24 h, 72 h, and five days to determine tissue damage. Findings/Results: The findings indicated that MDA levels in the brainstem were 46.29 ± 1.64 µM in the RAD group and decreased in the VC group (31.66 ± 1.72 µM). ALA pretreatment reduced MDA levels while simultaneously increasing SOD and CAT activity and TAC levels (60.26 ± 5.47 U/mL, 71.73 ± 2.88 U/mL, and 227.31 ± 9.40 mol/L, respectively). The greatest pathological changes in the rat's brainstems were seen in RAD animals compared to the VC group after 24 h, 72 h, and 5 days. As a result, karyorrhexis, pyknosis, vacuolization, and Rosenthal fibers vanished in the RAL group in three periods. Conclusion and implications: ALA exhibited substantial neuroprotectivity following radiation-induced brainstem damage.

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.

The Effect of Prostate Cancer Radiotherapy on Testosterone Level: A Systematic Review and Meta-analysis.

INTRODUCTION: In the current study, a systematic search and meta-analysis were performed to evaluate the effect of prostate cancer radiotherapy on testosterone levels of patients. METHODS: To illuminate the effect of radiotherapy on the testosterone level of prostate cancer patients, a systematic search was conducted in accordance with the PRISMA guideline in electronic databases of Scopus, Embase, PubMed, Web of Science, and clinical trials up to December 2018 using relevant keywords. Based on a certain set of inclusion and exclusion criteria, 12 eligible studies that had data on the testosterone level following prostate cancer radiotherapy were included in the meta-analysis. RESULTS: According to the various techniques of prostate cancer radiotherapy, the dose values scattered to the testicular tissues ranged from 0.31 to 10 Gy. Combining the findings from 12 studies, it was found that prostate cancer radiotherapy leads to a significant reduction in the testosterone level (Weighted Mean Difference [WMD]: -51.38 ng/dL, 95% CI: -75.86, -26.90, I2=0.0%, P<0.05). Furthermore, subgroup analysis by the patient number showed a significant reduction in the testosterone level at patient number < 50 (WMD: -80.32 ng/dL, 95% CI: -125.10, -35.55, I2= 0.0%) and 50 < patient number < 100 (WMD: -46.99 ng/dL, 95% CI: - 87.15, -6.82, I2= 0.0%). Subgroup analysis based on treatment technique type revealed a significant reduction in testosterone level after conventional radiotherapy (WMD: -56.67, 95% CI: -100.45,-12.88, I2= 34.3%) and IMRT/SBRT technique (WMD: -57.42, 95% CI: -99.39, -15.46, I2= 0.0%) in comparison with the proton therapy (WMD: 0.00, 95% CI: -80.24, 80.24). CONCLUSION: The findings showed a significant decrease in the testosterone level of prostate cancer patients after radiotherapy compared with pre-treatment levels.