Department of Medical Physics and Radiology, Faculty of Paramedical Sciences, Kashan University of Medical Sciences, Kashan, Iran.
Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran.
J Cell Physiol. 2020 Nov;235(11):8791-8798. doi: 10.1002/jcp.29722. Epub 2020 Apr 23.
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.
本研究旨在探讨褪黑素对 Wistar 大鼠脑干区域辐射诱导凋亡和氧化应激的影响。因此，动物接受了全脑 X 射线照射，单次剂量为 25Gy，并在存在或不存在 100mg/kgBW 褪黑素预处理的情况下进行照射。将大鼠分为四组（每组 10 只）：即载体对照组（VC）、100mg/kg 褪黑素组（MLT）、单纯照射组（RAD）和照射加 100mg/kg 褪黑素组（RAM）。照射前 1 小时，动物接受腹腔内（IP）褪黑素注射，6 小时后处死，然后测量脑干组织中一氧化氮（NO）、丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）、过氧化氢酶（CAT）和总抗氧化能力（TAC）的水平。此外，还采用 Western blot 分析技术评估 caspase-3 的表达水平。结果显示，与 VC 组相比，RAD 组大鼠脑干组织中 MDA 和 NO 水平显著升高（p<0.001）。此外，与 VC 组相比，照射大鼠 CAT、SOD、GPx 和 TAC 水平显著降低（p<0.01，p<0.001，p<0.001 和 p<0.001）。凋亡评估结果显示，与 VC 组相比，RAD 组 caspase-3 的表达水平显著升高（p<0.001）。褪黑素预处理通过降低 MDA 和 NO 水平（p<0.001）和增加抗氧化酶活性（p<0.001）减轻了辐射引起的不良反应。因此，与 RAD 组相比，RAM 组 caspase-3 蛋白表达水平显著降低（p<0.001）。总之，褪黑素在管理大鼠脑干中辐射诱导的氧化应激和凋亡方面表现出一定的神经保护活性；然而，褪黑素作为神经保护剂在人类中的应用需要进一步研究，特别是临床试验。
