Wang Hong, Sim Meng-Kwoon, Loke Weng Keong, Chinnathambi Arunachalam, Alharbi Sulaiman Ali, Tang Feng Ru, Sethi Gautam
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of SingaporeSingapore, Singapore.
Singapore Nuclear Research and Safety Initiative, National University of SingaporeSingapore, Singapore.
Front Pharmacol. 2017 Jun 16;8:352. doi: 10.3389/fphar.2017.00352. eCollection 2017.
This study was aimed to evaluate the possible protective effects of ursolic acid (UA) against gamma radiation induced damage both as well as . It was observed that the exposure to gamma radiation dose- and time-dependently caused a significant decrease in the cell viability, while the treatment of UA attenuated this cytotoxicity. The production of free radicals including reactive oxygen species (ROS) and NO increased significantly post-irradiation and further induced lipid peroxidation and oxidative DNA damage in cells. These deleterious effects could also be effectively blocked by UA treatment. In addition, UA also reversed gamma irradiation induced inflammatory responses, as indicated by the decreased production of TNF-α, IL-6, and IL-1β. NF-κB signaling pathway has been reported to be a key mediator involved in gamma radiation-induced cellular damage. Our results further demonstrated that gamma radiation dose- and time-dependently enhanced NF-κB DNA binding activity, which was significantly attenuated upon UA treatment. The post-irradiation increase in the expression of both phospho-p65, and phospho-IκBα was also blocked by UA. Moreover, the treatment of UA was found to significantly prolong overall survival in mice exposed to whole body gamma irradiation, and reduce the excessive inflammatory responses. Given its radioprotective efficacy as described here, UA as an antioxidant and NF-κB pathway blocker, may function as an important pharmacological agent in protecting against gamma irradiation-induced injury.
本研究旨在评估熊果酸（UA）对γ辐射诱导损伤的可能保护作用。结果发现，γ辐射暴露剂量和时间依赖性地导致细胞活力显著下降，而UA处理可减轻这种细胞毒性。包括活性氧（ROS）和一氧化氮（NO）在内的自由基产生在辐照后显著增加，并进一步诱导细胞内脂质过氧化和氧化性DNA损伤。这些有害影响也可被UA处理有效阻断。此外，UA还逆转了γ辐射诱导的炎症反应，表现为肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）产生减少。据报道，核因子-κB（NF-κB）信号通路是参与γ辐射诱导细胞损伤的关键介质。我们的结果进一步表明，γ辐射剂量和时间依赖性地增强NF-κB DNA结合活性，而UA处理可显著减弱这种活性。辐照后磷酸化p65和磷酸化IκBα表达的增加也被UA阻断。此外，发现UA处理可显著延长全身γ辐射小鼠的总生存期，并减少过度的炎症反应。鉴于此处所述的辐射防护功效，UA作为一种抗氧化剂和NF-κB通路阻断剂，可能作为一种重要的药理剂来预防γ辐射诱导的损伤。
