Grossini Elena, De Marchi Fabiola, Venkatesan Sakthipriyan, Mele Angelica, Ferrante Daniela, Mazzini Letizia
Laboratory of Physiology, Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy.
ALS Center, Neurology Unit, Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy.
Antioxidants (Basel). 2023 Oct 20;12(10):1887. doi: 10.3390/antiox12101887.
Oxidative stress, the alteration of mitochondrial function, and the neurovascular unit (NVU), play a role in Amyotrophic Lateral Sclerosis (ALS) pathogenesis. We aimed to demonstrate the changes in the plasma redox system and nitric oxide (NO) in 32 new ALS-diagnosed patients in treatment with Acetyl-L-Carnitine (ALCAR) compared to healthy controls. We also evaluated the effects of plasma on human umbilical cord-derived endothelial vascular cells (HUVEC) and astrocytes. The analyses were performed at the baseline (T0), after three months (T1), and after six months (T2). In ALS patients at T0/T1, the plasma markers of lipid peroxidation, thiobarbituric acid reactive substances (TBARS) and 4-hydroxy nonenal (4-HNE) were higher, whereas the antioxidants, glutathione (GSH) and the glutathione peroxidase (GPx) activity were lower than in healthy controls. At T2, plasma TBARS and 4-HNE decreased, whereas plasma GSH and the GPx activity increased in ALS patients. As regards NO, the plasma levels were firmly lower at T0-T2 than those of healthy controls. Cell viability, and mitochondrial membrane potential in HUVEC/astrocytes treated with the plasma of ALS patients at T0-T2 were reduced, while the oxidant release increased. Those results, which confirmed the fundamental role of oxidative stress, mitochondrial function, and of the NVU in ALS pathogenesis, can have a double meaning, acting as disease markers at baseline and potential markers of drug effects in clinical practice and during clinical trials.
氧化应激、线粒体功能改变以及神经血管单元（NVU）在肌萎缩侧索硬化症（ALS）发病机制中发挥作用。我们旨在证明32例新诊断为ALS且正在接受乙酰-L-肉碱（ALCAR）治疗的患者与健康对照相比，其血浆氧化还原系统和一氧化氮（NO）的变化。我们还评估了血浆对人脐带来源的血管内皮细胞（HUVEC）和星形胶质细胞的影响。分析在基线（T0）、三个月后（T1）和六个月后（T2）进行。在ALS患者的T0/T1期，脂质过氧化的血浆标志物硫代巴比妥酸反应性物质（TBARS）和4-羟基壬烯醛（4-HNE）较高，而抗氧化剂谷胱甘肽（GSH）和谷胱甘肽过氧化物酶（GPx）活性低于健康对照。在T2期，ALS患者血浆中的TBARS和4-HNE降低，而血浆GSH和GPx活性增加。关于NO，T0 - T2期的血浆水平始终低于健康对照。用T0 - T2期ALS患者血浆处理的HUVEC/星形胶质细胞的细胞活力和线粒体膜电位降低，而氧化剂释放增加。这些结果证实了氧化应激、线粒体功能和NVU在ALS发病机制中的重要作用，可能具有双重意义，在基线时可作为疾病标志物，在临床实践和临床试验中可作为药物作用的潜在标志物。
