Cytotoxicity and proliferative capacity impairment induced on human brain cell cultures after short- and long-term exposure to magnetite nanoparticles

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• 作者：Teresa Coccini ; Francesca Caloni ; Lenin Javier Ramí ; rez Cando and Uliana De Simone
• 刊名：Journal of Applied Toxicology
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：37
• 期：3
• 页码：361-373
• 全文大小：1445K
• ISSN：1099-1263

文摘

Since magnetic iron oxide nanoparticles (IONP) as magnetite (Fe₃O₄NPs) have potential applications in life sciences, industrial fields and biomedical care, the risks for occupational, general population and patients rises correspondingly. Excessive IONP accumulation in central nervous system (CNS) cells can lead to a disruption of normal iron metabolism/homeostasis, which is a characteristic hallmark resembling that of several neurodegenerative disorders. Fe₃O₄NPs- versus Fe₃O₄ bulk-induced toxic effects have been assessed in two human CNS cells namely astrocytes (D384) and neurons (SH-SY5Y) after short-term exposure (4–24-48 h) to 1–100 μg ml⁻¹, and long-term exposure to lower concentrations. Short-term Fe₃O₄NPs induced significant concentration- and time-dependent alterations of mitochondrial function in D384 (25–75% cell viability decrease): effects started at 25 μg ml⁻¹ after 4 h, and 1 μg ml⁻¹ after 48 h. SH-SY5Y were less susceptible: cytotoxicity occurred after 48 h only with 35–45% mortality (10–100 μg ml⁻¹). Accordingly, a more marked intracellular iron accumulation was observed in astrocytes than neurons. Membrane integrity was unaltered in both CNS cell types. Lowering Fe₃O₄NP concentrations (0.05–10 μg ml⁻¹) and prolonging the exposure time (up to 10 days), D384 toxicity was again observed (colony number decrease at ≥0.05 μg ml⁻¹, morphology alterations and colony size reduction at ≥0.5 μg ml⁻¹). Effects on SH-SY5Y appeared at the highest concentration only. Fe₃O₄ bulk was always remarkably toxic toward both cells. In summary, human cultured astrocytes were susceptible to both Fe₃O₄NP and bulk forms following short-term and extended exposure to low concentrations, while neurons were more resistant to NPs. Cellular iron overload may trigger adverse responses by releasing iron ions (particularly in astrocytes) thus compromising the normal functions of CNS. Copyright