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

Teresa Coccini, Francesca Caloni, Lenin Javier Ramírez Cando, Uliana De Simone

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19 Citations (Scopus)

Abstract

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 (4-24-48h) to 1-100μgml-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 25μgml-1 after 4h, and 1μgml-1 after 48h. SH-SY5Y were less susceptible: cytotoxicity occurred after 48 h only with 35-45% mortality (10-100μgml-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 (0.05-10μgml-1) and prolonging the exposure time (up to 10days), D384 toxicity was again observed (colony number decrease at ≥0.05μgml-1, morphology alterations and colony size reduction at ≥0.5μgml-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.

Original languageEnglish
JournalJournal of Applied Toxicology
DOIs
Publication statusPublished - Mar 2017

Fingerprint

Magnetite Nanoparticles
Neurology
Cytotoxicity
Cell culture
Astrocytes
Brain
Iron
Central Nervous System
Cell Culture Techniques
Neurons
Poisons
Ferrosoferric Oxide
Nanoparticles
Iron Overload
Biological Science Disciplines
Metabolism
Neurodegenerative Diseases
Toxicity
Cell Survival
Homeostasis

Keywords

  • CNS
  • D384 astrocytes
  • Iron
  • Nanoparticles
  • Safety
  • SH-SY5Y neurons

ASJC Scopus subject areas

  • Toxicology

Cite this

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title = "Cytotoxicity and proliferative capacity impairment induced on human brain cell cultures after short- and long-term exposure to magnetite nanoparticles",
abstract = "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 (4-24-48h) to 1-100μgml-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 25μgml-1 after 4h, and 1μgml-1 after 48h. SH-SY5Y were less susceptible: cytotoxicity occurred after 48 h only with 35-45{\%} mortality (10-100μgml-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 (0.05-10μgml-1) and prolonging the exposure time (up to 10days), D384 toxicity was again observed (colony number decrease at ≥0.05μgml-1, morphology alterations and colony size reduction at ≥0.5μgml-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.",
keywords = "CNS, D384 astrocytes, Iron, Nanoparticles, Safety, SH-SY5Y neurons",
author = "Teresa Coccini and Francesca Caloni and {Ram{\'i}rez Cando}, {Lenin Javier} and {De Simone}, Uliana",
year = "2017",
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T1 - Cytotoxicity and proliferative capacity impairment induced on human brain cell cultures after short- and long-term exposure to magnetite nanoparticles

AU - Coccini, Teresa

AU - Caloni, Francesca

AU - Ramírez Cando, Lenin Javier

AU - De Simone, Uliana

PY - 2017/3

Y1 - 2017/3

N2 - 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 (4-24-48h) to 1-100μgml-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 25μgml-1 after 4h, and 1μgml-1 after 48h. SH-SY5Y were less susceptible: cytotoxicity occurred after 48 h only with 35-45% mortality (10-100μgml-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 (0.05-10μgml-1) and prolonging the exposure time (up to 10days), D384 toxicity was again observed (colony number decrease at ≥0.05μgml-1, morphology alterations and colony size reduction at ≥0.5μgml-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.

AB - 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 (4-24-48h) to 1-100μgml-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 25μgml-1 after 4h, and 1μgml-1 after 48h. SH-SY5Y were less susceptible: cytotoxicity occurred after 48 h only with 35-45% mortality (10-100μgml-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 (0.05-10μgml-1) and prolonging the exposure time (up to 10days), D384 toxicity was again observed (colony number decrease at ≥0.05μgml-1, morphology alterations and colony size reduction at ≥0.5μgml-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.

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KW - Iron

KW - Nanoparticles

KW - Safety

KW - SH-SY5Y neurons

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