关键词: AKT GSK‐3β Notch‐1 Nrf2 gallic acid radiation

来  源:   DOI:10.1002/tox.24361

Abstract:
Despite the therapeutic advances in treating malignancies, the efficient radiotherapeutic approaches with deprived adverse reactions still represent a potential clinical inquiry. The current study aims to elucidate the role of gallic acid (GA) in modifying the hazardous renal cytotoxicity induced by acute exposure to radiation. The MTT test was used to evaluate the viability of Vero cells exposed to 2 Gy gamma radiation with or without incubation of GA. In an in vivo model, male Wistar rats were divided into four experimental groups (n = 6): Control, Irradiated (IRR, 5 Gy), GA (100 mg/kg, i.p.) + IRR, and Glycogen synthase kinase inhibitor (GSKI, 3 mg/kg, i.p.) + IRR. Based on the MTT toxicity assay, from 0 and up to 5 μM dosages of GA did not demonstrate any cytotoxicity to Vero cells. The optimal GA dose that could protect the cells from radiation was 5 μM. Furthermore, GA exerted a protective effect from gamma radiation on renal tissue as indicated by corrected renal functions, decreased LDH level in serum, and balanced oxidative status, which is indicated by decreased tissue contents of NOx and TBARS with a significant increase of reduced GSH. These outcomes were inferred by the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) expression. The overall molecular impact of radiation in damaging the renal tissue may be explained by modifying the upstream AKT activity and its downstream targets GSK-3β/Notch-1. Here, we concluded that the anticipated adverse reaction in the course of radiation exposure could be protected by daily administration of GA.
摘要:
尽管在治疗恶性肿瘤方面取得了进展,缺乏不良反应的有效放射治疗方法仍然是潜在的临床研究。本研究旨在阐明没食子酸(GA)在改变急性辐射引起的有害肾细胞毒性中的作用。使用MTT测试来评估在有或没有GA孵育的情况下暴露于2Gyγ辐射的Vero细胞的活力。在体内模型中,雄性Wistar大鼠分为四个实验组(n=6):对照组,辐照(IRR,5Gy),GA(100mg/kg,i.p.)+内部收益率,和糖原合成酶激酶抑制剂(GSKI,3mg/kg,i.p.)+内部收益率。基于MTT毒性试验,从0到5μM剂量的GA没有显示出对Vero细胞的任何细胞毒性。可以保护细胞免受辐射的最佳GA剂量为5μM。此外,如校正的肾功能所示,GA对肾组织具有γ辐射的保护作用,血清LDH水平降低,和平衡的氧化状态,这表明NOx和TBARS的组织含量降低,GSH的还原显着增加。这些结果是通过核因子红系2相关因子2(Nrf2)表达的上调来推断的。辐射在损害肾组织中的整体分子影响可以通过改变上游AKT活性及其下游靶标GSK-3β/Notch-1来解释。这里,我们得出的结论是,每天服用GA可以保护辐射暴露过程中的预期不良反应。
公众号