Chamorro Beatriz, Izquierdo-Bermejo Sara, Martín-de-Saavedra María Dolores, López-Muñoz Francisco, Chioua Mourad, Marco-Contelles José, Oset-Gasque María Jesús
Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal s/n, Ciudad Universitaria, 28040 Madrid, Spain.
Faculty of Health, Camilo José Cela University, Villanueva de la Cañada, 28692 Madrid, Spain.
Antioxidants (Basel). 2023 Jun 29;12(7):1364. doi: 10.3390/antiox12071364.
Ischemic stroke is the leading cause of disability and the second leading cause of death worldwide. However, current therapeutic strategies are scarce and of limited efficacy. The abundance of information available on the molecular pathophysiology of ischemic stroke has sparked considerable interest in developing new neuroprotective agents that can target different events of the ischemic cascade and may be used in combination with existing treatments. In this regard, nitrones represent a very promising alternative due to their renowned antioxidant and anti-inflammatory effects. In this study, we aimed to further investigate the neuroprotective effects of two nitrones, cholesteronitrone 2 () and quinolylnitrone 23 (), which have previously shown great potential for the treatment of stroke. Using an experimental in vitro model of cerebral ischemia, we compared their anti-necrotic, anti-apoptotic, and antioxidant properties with those of three reference compounds. Both and demonstrated significant neuroprotective effects (EC = 0.66 ± 0.23 μM and EC = 2.13 ± 0.47 μM, respectively) comparable to those of homo-bis-nitrone 6 () and N-acetylcysteine () and superior to those of α-phenyl-N-tert-butylnitrone (). While primarily derived from the nitrones' anti-necrotic capacities, their anti-apoptotic effects at high concentrations and antioxidant powers-especially in the case of -also contribute to their neuroprotective effects.
缺血性中风是全球致残的主要原因，也是第二大致死原因。然而，目前的治疗策略匮乏且疗效有限。关于缺血性中风分子病理生理学的大量信息引发了人们对开发新型神经保护剂的浓厚兴趣，这些药物可以针对缺血级联反应的不同环节，并可与现有治疗方法联合使用。在这方面，硝酮因其著名的抗氧化和抗炎作用而成为一个非常有前景的选择。在本研究中，我们旨在进一步研究两种硝酮，胆固醇硝酮2（）和喹啉硝酮23（）的神经保护作用，这两种硝酮先前已显示出治疗中风的巨大潜力。我们使用脑缺血的体外实验模型，将它们的抗坏死、抗凋亡和抗氧化特性与三种参考化合物进行了比较。和均表现出显著的神经保护作用（EC分别为0.66±0.23μM和2.13±0.47μM），与同型双硝酮6（）和N-乙酰半胱氨酸（）相当，且优于α-苯基-N-叔丁基硝酮（）。虽然它们的神经保护作用主要源于硝酮的抗坏死能力，但它们在高浓度时的抗凋亡作用和抗氧化能力——尤其是在的情况下——也对其神经保护作用有贡献。
