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Abstracts / Toxicology Letters 258S (2016) S62–S324
P17-002 Functionalization of nanostructured vanadium zerconium metal complex: Shifting the risk-benefit ratio M.E. Elnaggar 1,∗ , M. Wahba 2 , S.A. El Shebiney 1 , A.F. Galal 1 , N.A. Salem 1 1
Department of Narcotics, Ergogenics and Poisons, National Research Centre, Giza, Egypt 2 Department of Inorganic Chemistry, National Research Centre, Egypt
Vanadium is an important micronutrient with multiple beneficial biological activities. However, it has limited medicinal applications for its high toxicity. Structuring materials at nanoscale provide more effectiveness, low systemic toxicity, targeted delivery and controlled release of the material. The present study was conducted to investigate the effect of the novel nanostructured vanadium zerconium against lipopolysaccharide (LPS) induced acute liver damage. Lps was used in a dose of 10 ␮g/kg, intraperitoneally. The hepatic tissue was insulted and showed high FAB and MLC reactivity. Blood aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were elevated. Apoptotic and necrotic changes in hepatocytes were observed. Treatment with VnZrO showed protective effect and minimal toxic effect was demonstrated in DNA fragmentation test. Moreover, oxidative markers were leveled down and the antioxidant GSH pool was restored. This study elucidated the possible advantage of nanostructured metal based materials for inflammatory conditions. However, further toxicological investigation is needed to weigh its real beneficial actions. P17-003 Long term accumulation of gold nanoparticles in cells triggers the inhibition of macropinocytosis to reduce intracellular stress levels N. Gunduz 1,∗ , H. Ceylan 2 , M.O. Guler 1 , A.B. Tekinay 1 1
Department of Materials Science and Nanotechnology, Bilkent University, Ankara, Turkey 2 Max-Planck Institute for Intelligent Systems, Stuttgart, Germany The characterization of nanoparticle toxicity is typically limited to short-term cell viability assays and long-term systemic studies in animals, with little information on how these materials are processed on the cellular level under prolonged exposure. Consequently, there is a current lack of understanding regarding the entry, exclusion and sequestration pathways involved in the accumulation of nanoparticles, the investigation of which is of fundamental importance for the adequate assessment of nanomaterial toxicity. Here, we detail the accumulation patterns and response mechanisms associated with a sub-toxic dose of gold nanoparticles (AuNPs) in vascular endothelial cells over a two-month period, and report that AuNP entry is blocked through the inhibition of macropinocytosis but not caveolin- or clathrin-mediated endocytosis in these cells. In addition, fluctuations in the accumulation of AuNPs correspond to increases in intracellular stress marker, suggesting that AuNP exclusion occurs to reduce proteolytic stress. No cell death or increase in reactive oxygen species (ROS) was detected during the period of exposure, and the reduction of nanoparticle toxicity is likely to occur through the dilution of AuNP burden
by mitosis. We also present a general model for AuNP accumulation consistent with our observations in endothelial cells, which may provide significant insight regarding the impact of long-term nanoparticle exposure and accumulation in living systems. P17-004 Comparative in vitro cytotoxicity of citrate-coated silver nanoparticles on skin, liver and blood cell lines V. Bastos 1 , J. Carrola 2 , I.F. Duarte 2 , C. Santos 3 , H. Oliveira 1,∗ 1
CESAM & Department of Biology, University of Aveiro, Portugal CICECO – Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Aveiro, Portugal 3 Department of Biology, Faculty of Sciences, University of Porto, Rua do Campo Alegre, Porto, Portugal 2
Silver nanoparticles (AgNPs) have very efficient antimicrobial activity, which has encouraged their widespread use in a range of applications from medicine to industry, household, personal care products and clothing. In this study, the cytotoxicity of 30 nm AgNPs coated with citrate on the cell lines RAW 264.7, HepG2 and HaCaT was evaluated by assessing cell viability, reactive oxygen species (ROS) and cell cycle dynamics, 24 h after exposure. The human hepatoma cell line HepG2 was the most sensitive (IC50 of 11 ␮g/mL), while the macrophage cell line RAW 264.7 was the less sensitive (IC50 of 75 ␮g/mL). An increase in ROS levels was found for HaCaT cells upon exposure to IC50 dose, while exposure to IC20 did not induce changes in ROS levels. However, for RAW 264.7 cells a decrease in the ROS was detected upon exposure to IC20. The putative involvement of ROS in the high tolerance of these cells to citrate-AgNPs is hypothesized. For all cell lines, impairment of cell cycle was detected, specifically an arrest at G2 phase was observed for HaCaT and HepG2. Altogether our results show that the toxicity of AgNPs varies within the cell type, being, HepG2 the most sensitive to AgNPs, followed by HaCaT cells and finally RAW 264.7. This study supports the claim for more thorough studies on different cell types before a decision can be reached on the toxicity of nanoparticles. Acknowledgements: Funding to the project FCOMP-010124-FEDER-021456 (FCT PTDC/SAU-TOX/120953/2010), FCT grants (SFRH/BD/81792/2011, SFRH/BD/79494/2011, SFRH/BPD/ 111736/2015) and IFD ‘Investigador FCT’2014 contract are acknowledged. P17-005 Copper (II) oxide nanoparticles induce high toxicity in human neuronal cell M. Abudayyak 1,∗ , E. Guzel 2 , G. Ozhan 3 1
Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Karadeniz Technical University, Trabzon, Turkey 2 Department of Histology and Embryology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey 3 Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey Owing to antimicrobial, electron correlation effects, conductivity and other properties; Copper (II) oxide nanoparticles (CuO-NPs) have great importance in industrial and medical applications and
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