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Zinc oxide nanoparticles interfere with zinc ion homeostasis to cause cytotoxicity.
Toxicol Sci. 2012 Feb; 125(2):462-72.TS

Abstract

The toxicological effects of zinc oxide nanoparticles (ZnO-NPs) are attracting increasing concern as the field of nanotechnology progresses. Although the literature suggests that toxicity of ZnO-NPs may be related to their dissolution, the mechanism for ZnO-NP perturbation of cytosolic zinc concentration ([Zn(2+)](c)) homeostasis remains obscure. Using FluoZin-3 and RhodZin-3, this study investigated changes in both [Zn(2+)](c) and mitochondrial free Zn(2+) concentration ([Zn(2+)](m)) under conditions of ZnO-NP treatment in vivo and in vitro. In human leukemia Jurkat cells and human lung carcinoma H1355 cells, ZnO-NP treatment resulted in an elevation of both [Zn(2+)](c) and [Zn(2+)](m). In H1355 cells, ZnO-NP treatment induced depolarization of mitochondrial membrane potential, as well as caspase-3 activation and lactic dehydrogenase (LDH) release. In our in vivo experiments, when rats were exposed to ZnO-NPs, higher [Zn(2+)](c) and [Zn(2+)](m) were recorded in both broncho-alveolar lavage (BAL) cells and white blood cells isolated from ZnO-NP-exposed rats, compared with high efficiency particulate air-filter-protected controls LDH levels were also elevated in the BAL of ZnO-NP-exposed rats compared with controls. A mechanical toxicological pathway for ZnO-NP toxicity is suggested by these results: an elevation in [Zn(2+)](c) resulting from ZnO-NP dissolution in the intracellular endosome; cytosolic Zn(2+) sequestration by mitochondria; and elevated [Zn(2+)](m) leading to mitochondrial dysfunction, caspase activation, and cell apoptosis. We conclude that exposure to ZnO-NPs interferes with the homeostasis of [Zn(2+)](c,) and that elevated [Zn(2+)](c) results in cell apoptosis.

Authors+Show Affiliations

Department of Microbiology, Soochow University, Taipei, Taiwan, Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22112499

Citation

Kao, Yi-Yun, et al. "Zinc Oxide Nanoparticles Interfere With Zinc Ion Homeostasis to Cause Cytotoxicity." Toxicological Sciences : an Official Journal of the Society of Toxicology, vol. 125, no. 2, 2012, pp. 462-72.
Kao YY, Chen YC, Cheng TJ, et al. Zinc oxide nanoparticles interfere with zinc ion homeostasis to cause cytotoxicity. Toxicol Sci. 2012;125(2):462-72.
Kao, Y. Y., Chen, Y. C., Cheng, T. J., Chiung, Y. M., & Liu, P. S. (2012). Zinc oxide nanoparticles interfere with zinc ion homeostasis to cause cytotoxicity. Toxicological Sciences : an Official Journal of the Society of Toxicology, 125(2), 462-72. https://doi.org/10.1093/toxsci/kfr319
Kao YY, et al. Zinc Oxide Nanoparticles Interfere With Zinc Ion Homeostasis to Cause Cytotoxicity. Toxicol Sci. 2012;125(2):462-72. PubMed PMID: 22112499.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Zinc oxide nanoparticles interfere with zinc ion homeostasis to cause cytotoxicity. AU - Kao,Yi-Yun, AU - Chen,Yi-Chun, AU - Cheng,Tsun-Jen, AU - Chiung,Yin-Mei, AU - Liu,Pei-Shan, Y1 - 2011/11/23/ PY - 2011/11/25/entrez PY - 2011/11/25/pubmed PY - 2012/5/18/medline SP - 462 EP - 72 JF - Toxicological sciences : an official journal of the Society of Toxicology JO - Toxicol Sci VL - 125 IS - 2 N2 - The toxicological effects of zinc oxide nanoparticles (ZnO-NPs) are attracting increasing concern as the field of nanotechnology progresses. Although the literature suggests that toxicity of ZnO-NPs may be related to their dissolution, the mechanism for ZnO-NP perturbation of cytosolic zinc concentration ([Zn(2+)](c)) homeostasis remains obscure. Using FluoZin-3 and RhodZin-3, this study investigated changes in both [Zn(2+)](c) and mitochondrial free Zn(2+) concentration ([Zn(2+)](m)) under conditions of ZnO-NP treatment in vivo and in vitro. In human leukemia Jurkat cells and human lung carcinoma H1355 cells, ZnO-NP treatment resulted in an elevation of both [Zn(2+)](c) and [Zn(2+)](m). In H1355 cells, ZnO-NP treatment induced depolarization of mitochondrial membrane potential, as well as caspase-3 activation and lactic dehydrogenase (LDH) release. In our in vivo experiments, when rats were exposed to ZnO-NPs, higher [Zn(2+)](c) and [Zn(2+)](m) were recorded in both broncho-alveolar lavage (BAL) cells and white blood cells isolated from ZnO-NP-exposed rats, compared with high efficiency particulate air-filter-protected controls LDH levels were also elevated in the BAL of ZnO-NP-exposed rats compared with controls. A mechanical toxicological pathway for ZnO-NP toxicity is suggested by these results: an elevation in [Zn(2+)](c) resulting from ZnO-NP dissolution in the intracellular endosome; cytosolic Zn(2+) sequestration by mitochondria; and elevated [Zn(2+)](m) leading to mitochondrial dysfunction, caspase activation, and cell apoptosis. We conclude that exposure to ZnO-NPs interferes with the homeostasis of [Zn(2+)](c,) and that elevated [Zn(2+)](c) results in cell apoptosis. SN - 1096-0929 UR - https://www.unboundmedicine.com/medline/citation/22112499/Zinc_oxide_nanoparticles_interfere_with_zinc_ion_homeostasis_to_cause_cytotoxicity_ L2 - https://academic.oup.com/toxsci/article-lookup/doi/10.1093/toxsci/kfr319 DB - PRIME DP - Unbound Medicine ER -