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Intravenous administration of silver nanoparticles causes organ toxicity through intracellular ROS-related loss of inter-endothelial junction.
Part Fibre Toxicol. 2016 Apr 29; 13:21.PF

Abstract

BACKGROUND

Administration of silver nanoparticles (AgNPs) to mice could result in their distribution and accumulation in multiple organs, with notable prominence in liver, lungs, and kidneys. However, how AgNPs transport through blood vesicular system to reach the target organs is unclear, and the precise differences in the mechanisms of toxicity between AgNPs and silver ions still remain elusive. In the present research, the pathological changes on these target organs with a focus on inter-endothelial junction was investigated to gain a new insight of AgNPs toxicity by comparing the mechanisms of action of AgNPs and AgNO3.

METHODS

We investigated the in vitro cytotoxicity of either citrated-coated AgNPs (10, 75, and 110 nm) or silver nitrate (AgNO3) following 24 h incubations (1-40 μg/mL) in the presence of primary human umbilical vein endothelial cells (HUVEC). Meanwhile, we detected the effects of AgNPs on intercellular conjunction and intracellular ROS by VE-cadherin staining and 2', 7'-dichlorodihydrofluorescein diacetate (DCFH-DA) assay, respectively. To assess in vivo toxicity, we administered single or multiple intravenous injections (25 μg Ag for AgNPs and 2.5 μg Ag for AgNO3 per dose) to mice.

RESULTS

In the in vitro study, the TEM observation showed that AgNPs were taken up by endothelial cells while AgNO3 was taken up little. Meanwhile AgNPs incubation induced the elevation of intracellular ROS and down-regulation of VE-cadherin between the endothelial cells and affected the cytoskeleton actin reorganization, which could be rescued by antioxidant N-acetylcysteine. In contrast, AgNO3 caused direct cell death when the concentration was higher than 20 μg/mL and without ROS induction at lower concentration. The release of AgNPs from leaking vessels induced peripheral inflammation in the liver, lungs, and kidneys, and the severity increased in proportion to the diameter of the AgNPs used.

CONCLUSION

It is AgNPs but not AgNO3 that were taken up by vascular endothelial cells and induced intracellular ROS elevated, which was closely related to disruption of the integrity of endothelial layer. The AgNPs-induced leakiness of endothelial cells could mediate the common peripheral inflammation in liver, kidney and lung through intravenous exposure.

Authors+Show Affiliations

Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, 72079, USA.Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.Center for Food Safety and Applied Nutrition, US Food and Drug Administration, College Park, MD, 20740, USA.Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. liujian@ibms.pumc.edu.cn.Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. xuhy@pumc.edu.cn.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

27129495

Citation

Guo, Hua, et al. "Intravenous Administration of Silver Nanoparticles Causes Organ Toxicity Through Intracellular ROS-related Loss of Inter-endothelial Junction." Particle and Fibre Toxicology, vol. 13, 2016, p. 21.
Guo H, Zhang J, Boudreau M, et al. Intravenous administration of silver nanoparticles causes organ toxicity through intracellular ROS-related loss of inter-endothelial junction. Part Fibre Toxicol. 2016;13:21.
Guo, H., Zhang, J., Boudreau, M., Meng, J., Yin, J. J., Liu, J., & Xu, H. (2016). Intravenous administration of silver nanoparticles causes organ toxicity through intracellular ROS-related loss of inter-endothelial junction. Particle and Fibre Toxicology, 13, 21. https://doi.org/10.1186/s12989-016-0133-9
Guo H, et al. Intravenous Administration of Silver Nanoparticles Causes Organ Toxicity Through Intracellular ROS-related Loss of Inter-endothelial Junction. Part Fibre Toxicol. 2016 Apr 29;13:21. PubMed PMID: 27129495.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intravenous administration of silver nanoparticles causes organ toxicity through intracellular ROS-related loss of inter-endothelial junction. AU - Guo,Hua, AU - Zhang,Jing, AU - Boudreau,Mary, AU - Meng,Jie, AU - Yin,Jun-jie, AU - Liu,Jian, AU - Xu,Haiyan, Y1 - 2016/04/29/ PY - 2015/10/03/received PY - 2016/04/18/accepted PY - 2016/5/1/entrez PY - 2016/5/1/pubmed PY - 2016/10/12/medline KW - Inter-endothelial junctions KW - Peripheral inflammation KW - ROS KW - Silver nanoparticles KW - Silver nitrate SP - 21 EP - 21 JF - Particle and fibre toxicology JO - Part Fibre Toxicol VL - 13 N2 - BACKGROUND: Administration of silver nanoparticles (AgNPs) to mice could result in their distribution and accumulation in multiple organs, with notable prominence in liver, lungs, and kidneys. However, how AgNPs transport through blood vesicular system to reach the target organs is unclear, and the precise differences in the mechanisms of toxicity between AgNPs and silver ions still remain elusive. In the present research, the pathological changes on these target organs with a focus on inter-endothelial junction was investigated to gain a new insight of AgNPs toxicity by comparing the mechanisms of action of AgNPs and AgNO3. METHODS: We investigated the in vitro cytotoxicity of either citrated-coated AgNPs (10, 75, and 110 nm) or silver nitrate (AgNO3) following 24 h incubations (1-40 μg/mL) in the presence of primary human umbilical vein endothelial cells (HUVEC). Meanwhile, we detected the effects of AgNPs on intercellular conjunction and intracellular ROS by VE-cadherin staining and 2', 7'-dichlorodihydrofluorescein diacetate (DCFH-DA) assay, respectively. To assess in vivo toxicity, we administered single or multiple intravenous injections (25 μg Ag for AgNPs and 2.5 μg Ag for AgNO3 per dose) to mice. RESULTS: In the in vitro study, the TEM observation showed that AgNPs were taken up by endothelial cells while AgNO3 was taken up little. Meanwhile AgNPs incubation induced the elevation of intracellular ROS and down-regulation of VE-cadherin between the endothelial cells and affected the cytoskeleton actin reorganization, which could be rescued by antioxidant N-acetylcysteine. In contrast, AgNO3 caused direct cell death when the concentration was higher than 20 μg/mL and without ROS induction at lower concentration. The release of AgNPs from leaking vessels induced peripheral inflammation in the liver, lungs, and kidneys, and the severity increased in proportion to the diameter of the AgNPs used. CONCLUSION: It is AgNPs but not AgNO3 that were taken up by vascular endothelial cells and induced intracellular ROS elevated, which was closely related to disruption of the integrity of endothelial layer. The AgNPs-induced leakiness of endothelial cells could mediate the common peripheral inflammation in liver, kidney and lung through intravenous exposure. SN - 1743-8977 UR - https://www.unboundmedicine.com/medline/citation/27129495/Intravenous_administration_of_silver_nanoparticles_causes_organ_toxicity_through_intracellular_ROS_related_loss_of_inter_endothelial_junction_ L2 - https://particleandfibretoxicology.biomedcentral.com/articles/10.1186/s12989-016-0133-9 DB - PRIME DP - Unbound Medicine ER -