Neurotoxicity mediated by oxidative stress caused by titanium dioxide nanoparticles in human neuroblastoma (SH-SY5Y) cells |
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| Institution: | 1. Center of Studies in Health and Environment, School of Science and Technology, National University of San Martín, San Martín, Buenos Aires, Argentina;2. National Council of Scientific and Technical Research (CONICET), Buenos Aires, Argentina;3. Universidad de Buenos Aires, Facultad de Odontología, Cátedra de Anatomía Patológica, Buenos Aires, Argentina;4. Research Fellow of the University of Buenos Aires, Buenos Aires, Argentina;5. Universidad de Buenos Aires, Facultad de Odontología, Cátedra de Histología y Embriología, Buenos Aires, Argentina;1. School of Life Science, Huaiyin Normal University, Huaian 223300, China;2. Medical College of Soochow University, Suzhou 215123, China;3. Library of Soochow University, Suzhou 215123, China;1. School of Environmental Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074, China;2. State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China;3. Graduate University of Chinese Academy of Sciences, Beijing 100039, China;4. College of Mechanical and Electronic Engineering, China University of Petroleum (East China), Qingdao 266580, China;1. Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;2. Medical Genetic Research Center (MGRC), School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;3. Immunology Research Center, Buali Institute, Mashhad University of Medical Sciences, Mashhad, Iran;4. Neurocognitive Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;1. Ministry of Education Key Laboratory of Molecular Microbiology and Technology, Department of Microbiology, College of Life Science, Nankai University, Tianjin 300071, China;2. Water Environment Monitoring Center of Yellow River Basin, Zhengzhou, Henan 450002, China |
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| Abstract: | BackgroundTitanium is widely used in biomedicine. Due to biotribocorrosion, titanium dioxide (TiO2) nanoparticles (NPs) can be released from the titanium implant surface, enter the systemic circulation, and migrate to various organs and tissues including the brain. A previous study showed that 5 nm TiO2 NPs reached the highest concentration in the brain. Even though TiO2 NPs are believed to possess low toxicity, little is known about their neurotoxic effects. The aim of the study was to evaluate in vitro the effects of 5 nm TiO2 NPs on a human neuroblastoma (SH-SY5Y) cell line.MethodsCell cultures were divided into non-exposed and exposed to TiO2 NPs for 24 h. The following were evaluated: reactive oxygen species (ROS) generation, apoptosis, cellular antioxidant response, endoplasmic reticulum stress and autophagy.ResultsExposure to TiO2 NPs induced ROS generation in a dose dependent manner, with values reaching up to 10 fold those of controls (p < 0.001). Nrf2 nuclear localization and autophagy, also increased in a dose dependent manner. Apoptosis increased by 4- to 10-fold compared to the control group, depending on the dose employed.ConclusionsOur results show that TiO2 NPs cause ROS increase, induction of ER stress, Nrf2 cytoplasmic translocation to the nucleus and apoptosis. Thus, neuroblastoma cell response to TiO2 NPs may be associated with an imbalance of the oxidative metabolism where endoplasmic reticulum-mediated signal pathway seems to be the main neurotoxic mechanism. |
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| Keywords: | Titanium Nanoparticles Oxidative stress Neurotoxicity Apoptosis |
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