title: Fe3 O4 nanoparticle redox system modulation via cell-cycle progression and gene expression in human mesenchymal stem cells.
abstract: The use of engineered nanoparticles (NPs) across multiple fields and applications has rapidly increased over the last decade owing to their unusual properties. However, there is an increased need in understanding their toxicological effect on human health. Particularly, iron oxide (Fe3 O4 ) have been used in various sectors, including biomedical, food, and agriculture, but the current understanding of their impact on human health is inadequate. In this investigation, we assessed the toxic effect of Fe3 O4 NPs on human mesenchymal stem cells (hMSCs) adopting cell viability, cellular morphological changes, mitochondrial transmembrane potential, and cell-cycle progression assessment methodologies. Furthermore, the expression of oxidative stress, cell death, and cell-cycle regulatory genes was assessed using quantitative polymerase chain reaction. The Fe3 O4 NPs induced cytotoxicity and nuclear morphological changes in hMSCs by dose and time exposure. Cell-cycle analysis indicated that Fe3 O4 NPs altered the cell-cycle progression through a decrease in the proportion of cells in the G0 -G1 phase. The hMSC mitochondrial membrane potential loss increased with an increase in the concentration of Fe3 O4 NPs exposure. The observed expression levels of the CYP1A, TNF3, TNFSF10, E2F1, and CCNC genes were significantly upregulated in hMSCs in response to Fe3 O4 NPs exposure. Our findings suggest that Fe3 O4 NPs caused metabolic stress through altered cell cycle, oxidative stress, and cell death regulatory gene expression in hMSCs. The results of this investigation revealed that Fe3 O4 NPs exhibited moderate toxicity on hMSCs and that Fe3 O4 NPs may have biomedical applications at low concentrations. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 901-912, 2016.
authors.affiliation: Department of Food Science and Nutrition, Nanobiotechnology and Molecular Biology Research Lab, College of Food Science and Agriculture, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Vaiyapuri S
authors.initials: VS
authors.lastname: Periasamy
authors.affiliation: Department of Food Science and Nutrition, Nanobiotechnology and Molecular Biology Research Lab, College of Food Science and Agriculture, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Jegan
authors.initials: J
authors.lastname: Athinarayanan
authors.affiliation: Department of Food Science and Nutrition, Nanobiotechnology and Molecular Biology Research Lab, College of Food Science and Agriculture, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Alhazmi
authors.affiliation: Department of Food Science and Nutrition, Nanobiotechnology and Molecular Biology Research Lab, College of Food Science and Agriculture, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Khalid A
authors.initials: KA
authors.lastname: Alatiah
authors.affiliation: Department of Food Science and Nutrition, Nanobiotechnology and Molecular Biology Research Lab, College of Food Science and Agriculture, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Alshatwi
mesh_terms: D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004785:Environmental Pollutants / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D058185:Magnetite Nanoparticles / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D004785:Environmental Pollutants; D058185:Magnetite Nanoparticles
keywords: Fe3O4 nanoparticles; cell cycle; cell death; mesenchymal stem cells; oxidative stress