Fe sub(3)O sub(4) nanoparticle redox system modulation via cell-cycle progression and gene expression in human mesenchymal stem cells

• Published in: Environmental toxicology 2016-08, Vol.31 (8), p.901-912
• Main Authors: Periasamy, Vaiyapuri S, Athinarayanan, Jegan, Alhazmi, Mohammad, Alatiah, Khalid A, Alshatwi, Ali A
• Format: Article
• Language: English
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.22098

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 (Fe sub(3)O sub(4)) 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 Fe sub(3)O sub(4) 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 Fe sub(3)O sub(4) NPs induced cytotoxicity and nuclear morphological changes in hMSCs by dose and time exposure. Cell-cycle analysis indicated that Fe sub(3)O sub(4) NPs altered the cell-cycle progression through a decrease in the proportion of cells in the G sub(0)-G sub(1) phase. The hMSC mitochondrial membrane potential loss increased with an increase in the concentration of Fe sub(3)O sub(4) NPs exposure. The observed expression levels of the CYP1A, TNF3, TNFSF10, E2F1, and CCNC genes were significantly upregulated in hMSCs in response to Fe sub(3)O sub(4) NPs exposure. Our findings suggest that Fe sub(3)O sub(4) 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 Fe sub(3)O sub(4) NPs exhibited moderate toxicity on hMSCs and that Fe sub(3)O sub(4) NPs may have biomedical applications at low concentrations. Environ Toxicol 31: 901-912, 2016.