苯丙胺和哌醋甲酯对 SH-SY5Y 细胞多巴胺能神经毒性的保护作用

IF 2.9 Q2 TOXICOLOGY Current Research in Toxicology Pub Date : 2024-01-01 DOI:10.1016/j.crtox.2024.100165
Patrícia Carneiro , Mariana Ferreira , Vera Marisa Costa , Félix Carvalho , João Paulo Capela
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引用次数: 0

摘要

帕金森病(Parkinson's disease,PD)是第二大最常见的神经退行性疾病,其全面治疗仍被认为是一项尚未满足的需求。由于苯丙胺(AMPH)和哌醋甲酯(MPH)这两种精神兴奋剂被证明对中风和其他神经元损伤疾病具有神经保护作用,本研究旨在评估它们在分化的人多巴胺能SH-SY5Y细胞中对6-羟基多巴胺(6-OHDA)和百草枯(PQ)这两种多巴胺能神经毒素的神经保护潜力。在暴露于治疗浓度的 AMPH 或 MPH(0.001-10 μM)24 小时后,细胞毒性和线粒体膜电位均未发生变化。另一方面,24 小时暴露于 6-OHDA(31.25-500 μM)或 PQ(100-5000 μM)会诱发浓度依赖性线粒体功能障碍(通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物(MTT)检测法评估)和溶酶体损伤(通过中性红吸收检测法评估)。在 MTT 试验中,根据浓度-毒性曲线得出的致死浓度 25 和 50,6-OHDA 为 99.9 µM 和 133.6 µM,PQ 为 422 µM 和 585.8 µM。两种毒物都会导致线粒体膜电位去极化,但只有 6-OHDA 会增加活性氧(ROS)。最重要的是,1 μM 的 AMPH 或 MPH 可部分阻止 PQ 诱导的毒性。根据这些发现,AMPH 和 MPH 可对 PQ 诱导的神经毒性提供一定的神经保护作用,但这种保护作用的确切机制还需要进一步研究。
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Protective effects of amphetamine and methylphenidate against dopaminergic neurotoxicants in SH-SY5Y cells

Full treatment of the second most common neurodegenerative disorder, Parkinson’s disease (PD), is still considered an unmet need. As the psychostimulants, amphetamine (AMPH) and methylphenidate (MPH), were shown to be neuroprotective against stroke and other neuronal injury diseases, this study aimed to evaluate their neuroprotective potential against two dopaminergic neurotoxicants, 6-hydroxydopamine (6-OHDA) and paraquat (PQ), in differentiated human dopaminergic SH-SY5Y cells.

Neither cytotoxicity nor mitochondrial membrane potential changes were seen following a 24-hour exposure to either therapeutic concentration of AMPH or MPH (0.001–10 μM). On the other hand, a 24-hour exposure to 6-OHDA (31.25–500 μM) or PQ (100–5000 μM) induced concentration-dependent mitochondrial dysfunction, assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, and lysosomal damage, evaluated by the neutral red uptake assay. The lethal concentrations 25 and 50 retrieved from the concentration-toxicity curves in the MTT assay were 99.9 µM and 133.6 µM for 6-OHDA, or 422 µM and 585.8 µM for PQ. Both toxicants caused mitochondrial membrane potential depolarization, but only 6-OHDA increased reactive oxygen species (ROS). Most importantly, PQ-induced toxicity was partially prevented by 1 μM of AMPH or MPH. Nonetheless, neither AMPH nor MPH could prevent 6-OHDA toxicity in this experimental model.

According to these findings, AMPH and MPH may provide some neuroprotection against PQ-induced neurotoxicity, but further investigation is required to determine the exact mechanism underlying this protection.

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来源期刊
Current Research in Toxicology
Current Research in Toxicology Environmental Science-Health, Toxicology and Mutagenesis
CiteScore
4.70
自引率
3.00%
发文量
33
审稿时长
82 days
期刊最新文献
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