An in vitro evaluation of the antioxidant activities of necroptosis and apoptosis inhibitors: the potential of necrostatin-1 and necrostatin-1i to have radical scavenging activities
An in vitro evaluation of the antioxidant activities of necroptosis and apoptosis inhibitors: the potential of necrostatin-1 and necrostatin-1i to have radical scavenging activities
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DOI：
10.1007/s43440-023-00450-y
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发表时间：
2023-01
影响因子：
4.4
通讯作者：
H. Ushijima;Rina Monzaki
中科院分区：
文献类型：
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作者：
H. Ushijima;Rina Monzaki
研究背景坏死抑制剂Necroptosis inhibitors，包括necrostatin-1（Nec-1），作为一种潜在的治疗药物，在治疗急性肺损伤、慢性阻塞性肺疾病、急性肾损伤、非酒精性脂肪肝和神经退行性疾病等方面受到广泛关注，其中坏死被认为是一个致病因素。Nec-1抑制necroptosis通过抑制受体相互作用蛋白（RIP）1激酶，也可以减少活性氧（ROS）的生产，但是，潜在的分子机制介导的ROS reduction仍然unclear.MethodsThe抗氧化作用的necroptosis抑制剂，包括Nec-1和凋亡抑制剂，进行定量的1，1-二苯基-2-苦肼基（DPPH）自由基清除试验。随后测定的铜离子还原能力和超氧化物歧化酶（SOD）-like activity.ResultsConsidering所有检查的细胞凋亡和坏死抑制剂，NEC-1和NEC-1 i显示抗氧化活性DPPH自由基清除试验。在铜离子还原能力测定中，Nec-1 i显示出比Nec-1更强的抗氧化能力。在SOD样活性测定中，Nec-1和Nec-1 i的抗氧化能力均强于抗坏血酸（IC 50分别为4.6 ± 0.040和61 ± 0.54 μM）。结论Nec-1和Nec-1 i可能具有直接清除超氧阴离子自由基的能力，而不依赖于RIP 1的抑制。
BackgroundNecroptosis inhibitors, including necrostatin-1 (Nec-1), are attracting attention as potential therapeutic agents against various diseases, such as acute lung injury, chronic obstructive pulmonary disease, acute kidney injury, nonalcoholic fatty liver, and neurodegenerative disease, where necroptosis is thought to act as a contributing factor. Nec-1 suppresses necroptosis by inhibiting receptor-interacting protein (RIP) 1 kinase and can also reduce reactive oxygen species (ROS) production; however, the underlying molecular mechanisms mediating ROS reduction remain unclear.MethodsThe antioxidant effects of necroptosis inhibitors, including Nec-1 and apoptosis inhibitors, were quantified by performing a 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay. Nec-1-related compounds were subsequently assayed for cupric ion-reducing capacity and superoxide dismutase (SOD)-like activity.ResultsConsidering all examined apoptosis and necroptosis inhibitors, Nec-1and Nec-1i exhibited antioxidant activity in DPPH radical scavenging assay. In the cupric ion-reducing capacity assay, Nec-1i showed stronger antioxidant capacity than Nec-1. In the SOD-like activity assay, both Nec-1 and Nec-1i were found to have stronger antioxidant capacity than ascorbic acid (IC50= 4.6 ± 0.040 and 61 ± 0.54 µM, respectively).ConclusionThese results suggest that Nec-1 and Nec-1i may exhibit direct radical scavenging ability against superoxide anions, independent of RIP1 inhibition.