College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, 32307, USA.
The National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL, 32310, USA.
Sci Rep. 2018 Feb 9;8(1):2710. doi: 10.1038/s41598-018-21182-7.
Cocaine is one of the powerful addictive drugs, widely abused in most Western countries. Because of high lipophilic nature, cocaine easily reaches various domains of the central nervous system (CNS) and triggers different levels of cellular toxicity. The aim of this investigation was to reproduce cocaine toxicity in differentiated PC12 cells through quantitative knowledge on biochemical and cytotoxicity markers. We differentiated the cells with 0.1 μg/ml nerve growth factor (NGF) for 5 days, followed by treatment with cocaine for 48 h at in vivo and in vitro concentrations. Results indicated that cocaine at in vivo concentrations neither killed the cells nor altered the morphology, but decreased the mitochondrial membrane potential that paralleled with increased lactate and glutathione (GSH) levels. On the other hand, cocaine at in vitro concentrations damaged the neurites and caused cell death, which corresponded with increased reactive oxygen species (ROS) generation, plasma membrane damage, and GSH depletion with no detectable nitric oxide (NO) level. While direct understanding of cocaine and cell interaction under in vivo animal models is impeded due to high complexity, our present in vitro results assisted in understanding the onset of some key events of neurodegenerative diseases in cocaine treated neuronal cells.
可卡因是一种强效成瘾性药物，在大多数西方国家被广泛滥用。由于其高亲脂性，可卡因很容易到达中枢神经系统（CNS）的各个区域，并引发不同程度的细胞毒性。本研究旨在通过对生化和细胞毒性标志物的定量知识，在分化的 PC12 细胞中重现可卡因毒性。我们用 0.1μg/ml 神经生长因子（NGF）分化细胞 5 天，然后用体内和体外浓度的可卡因处理 48 小时。结果表明，体内浓度的可卡因既没有杀死细胞，也没有改变细胞形态，但降低了线粒体膜电位，同时乳酸和谷胱甘肽（GSH）水平升高。另一方面，体外浓度的可卡因损伤了轴突并导致细胞死亡，这与活性氧（ROS）生成增加、质膜损伤和 GSH 耗竭相对应，而没有检测到一氧化氮（NO）水平。虽然由于高度复杂性，体内动物模型中可卡因和细胞相互作用的直接理解受到阻碍，但我们目前的体外结果有助于理解可卡因处理的神经元细胞中神经退行性疾病的一些关键事件的发生。
