Departamento de Bioquímica y Biología Molecular, Universidad de Córdoba, 14004 Córdoba, Spain.
J Physiol Biochem. 2009 Sep;65(3):291-6. doi: 10.1007/BF03180581.
In neurodegenerative diseases, progressive oxidative stress is a major event that precedes neuronal death. Oxidative stress is characterized by an imbalance between oxidants and antioxidants. This imbalance induced oxidative molecular and cell damage, reducing cellular viability. 3-Nitropropionic acid (3NP) causes oxidative stress and other molecular and cellular changes similar to those observed in neurons of patients with Huntington's disease. Since carvedilol and melatonin act as free-radical scavengers, this study examined the effect of carvedilol (10(-5) M) and melatonin (10(-5) M) on oxidative and cell damage induced by 3NP in N1E-115 neuroblastoma cells. Carvedilol and melatonin prevented the increases in lipid peroxidation and total LDH activity, as well as the depletion of reduced glutathione (GSH) and the reduction of antioxidative enzymes activities in N1E-115 cells incubated with 100 mM 3NP. All these carvedilol and melatonin effects were more intense when the drugs were added before rather than after inducing the damage by 3NP. These results also provided evidence supporting the hypothesis that carvedilol and melatonin can be useful for treating neurodegenerative diseases, such as Huntington's disease.
在神经退行性疾病中，进行性氧化应激是导致神经元死亡的主要事件。氧化应激的特征是氧化剂和抗氧化剂之间的不平衡。这种不平衡引起氧化的分子和细胞损伤，降低细胞活力。3-硝基丙酸（3NP）引起的氧化应激和其他分子和细胞变化类似于亨廷顿病患者神经元中观察到的变化。由于卡维地洛和褪黑素作为自由基清除剂，本研究探讨了卡维地洛（10（-5）M）和褪黑素（10（-5）M）对 3NP 在 N1E-115 神经母细胞瘤细胞中诱导的氧化和细胞损伤的影响。卡维地洛和褪黑素可防止脂质过氧化和总 LDH 活性增加，以及降低谷胱甘肽（GSH）水平和抗氧化酶活性降低，在 100mM 3NP 孵育的 N1E-115 细胞中。当药物在 3NP 诱导损伤之前而不是之后添加时，卡维地洛和褪黑素的所有这些作用都更加明显。这些结果也为卡维地洛和褪黑素可用于治疗亨廷顿病等神经退行性疾病的假说提供了证据。
