Biochemistry Laboratory, LR12ES05 Nutrition-Functional Foods and Vascular Health, Faculty of Medicine, University of Monastir, Monastir 5019, Tunisia.
Laboratory of Molecular Physiology, Faculty of Health and Life Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
Biomolecules. 2021 May 27;11(6):797. doi: 10.3390/biom11060797.
Oxysterols are assumed to be the driving force behind numerous neurodegenerative diseases. In this work, we aimed to study the ability of 7β-hydroxycholesterol (7β-OHC) to trigger oxidative stress and cell death in human neuroblastoma cells (SH-SY5Y) then the capacity of Nigella sativa and Milk thistle seed oils (NSO and MTSO, respectively) to oppose 7β-OHC-induced side effects. The impact of 7β-OHC, associated or not with NSO or MTSO, was studied on different criteria: cell viability; redox status, and apoptosis. Oxidative stress was assessed through the intracellular reactive oxygen species (ROS) production, levels of enzymatic and non-enzymatic antioxidants, lipid, and protein oxidation products. Our results indicate that 7β-OHC (40 µg/mL) exhibit pr-oxidative and pro-apoptotic activities shown by a decrease of the antioxidant enzymatic activities and an increase of ROS production, lipid, and protein oxidation end products as well as nitrotyrosine formation and caspase 3 activation. However, under the pre-treatment with NSO, and especially with MTSO (100 µg/mL), a marked attenuation of oxidative damages was observed. Our study suggests harmful effects of 7β-OHC consisting of pro-oxidative, anti-proliferative, and pro-apoptotic activities that may contribute to neurodegeneration. NSO and especially MTSO showed potential cytoprotection against the cytotoxicity of 7β-OHC.
氧化固醇被认为是许多神经退行性疾病的主要驱动力。在这项工作中，我们旨在研究 7β-羟胆固醇（7β-OHC）在人神经母细胞瘤细胞（SH-SY5Y）中引发氧化应激和细胞死亡的能力，然后研究黑种草籽油和乳蓟籽油（NSO 和 MTSO）分别）对抗 7β-OHC 诱导的副作用的能力。研究了 7β-OHC 及其与 NSO 或 MTSO 联合使用对不同标准的影响：细胞活力；氧化还原状态和细胞凋亡。通过细胞内活性氧（ROS）产生、酶和非酶抗氧化剂水平、脂质和蛋白质氧化产物来评估氧化应激。我们的结果表明，7β-OHC（40μg/mL）表现出促氧化和促凋亡活性，表现为抗氧化酶活性降低和 ROS 产生增加，脂质和蛋白质氧化终产物以及硝基酪氨酸形成和 caspase 3 激活增加。然而，在用 NSO 预处理，特别是用 MTSO（100μg/mL）预处理后，观察到氧化损伤明显减弱。我们的研究表明 7β-OHC 具有促氧化、抗增殖和促凋亡活性，可能导致神经退行性变。NSO 尤其是 MTSO 对 7β-OHC 的细胞毒性具有潜在的细胞保护作用。
