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Review of Zinc Oxide Nanoparticles: Toxicokinetics, Tissue Distribution for Various Exposure Routes, Toxicological Effects, Toxicity Mechanism in Mammals, and an Approach for Toxicity Reduction

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A Correction to this article was published on 14 April 2023

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Abstract

Zinc oxide (ZnO) nanoparticles (NPs) are widely used as a sunscreen, antibacterial agent, dietary supplement, food additive, and semiconductor material. This review summarizes the biological fate following various exposure routes, toxicological effects, and toxicity mechanism of ZnO NPs in mammals. Furthermore, an approach to reduce the toxicity and biomedical applications of ZnO NPs are discussed. ZnO NPs are mainly absorbed as Zn2+ and partially as particles. Regardless of exposure route, elevated Zn concentration in the liver, kidney, lungs, and spleen are observed following ZnO NP exposure, and these are the target organs for ZnO NPs. The liver is the main organ responsible for ZnO NP metabolism and the NPs are mainly excreted in feces and partly in urine. ZnO NPs induce liver damage (oral, intraperitoneal, intravenous, and intratracheal exposure), kidney damage (oral, intraperitoneal, and intravenous exposure) and lung injury (airway exposure). Reactive oxygen species (ROS) generation and induction of oxidative stress may be a major toxicological mechanism for ZnO NPs. ROS are generated by both excess Zn ion release and the particulate effect resulting from the semiconductor or electronic properties of ZnO NPs. ZnO NP toxicity can be reduced by coating their surface with silica, which prevents Zn2+ release and ROS generation. Due to their superior characteristics, ZnO NPs are expected to be used for biomedical applications, such as bioimaging, drug delivery, and anticancer agents, and surface coatings and modification will expand the biomedical applications of ZnO NPs further.

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Abbreviations

ZnO:

Zinc oxide

NPs:

Nanoparticles

8-OHdG:

8-Hydroxydeoxyguanosine

AST:

Aspartate transaminase

ALT:

Alanine transaminase

ALP:

Alkaline phosphatase

BUN:

Blood urea nitrogen

Cre:

Creatinine

IL1-β:

Interleukin1-β

LDH:

Lactate dehydrogenase

LD50 :

Lethal dose 50

MRT:

Mean residual time

MT:

Metallothionein

ROS:

Reactive oxygen species

TNF-α:

Tumor necrosis factor-α

IFN-γ:

Interferon-γ

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Acknowledgements

This work was supported by JSPS KAKENHI Grants-in-Aid for Scientific Research (B) [grant number 21H03212] and Grants-in-Aid for Young Scientists (A) [grant number 26713025] to JF. The authors acknowledge the cooperation of Prof. Y. Fujita, Prof. H. Takeshita, Dr. T. Miki, and Mr. R. Oono.

Funding

This work was supported by JSPS KAKENHI Grants-in-Aid for Scientific Research (B) [grant number 21H03212] and Grants-in-Aid for Young Scientists (A) [grant number 26713025] to JF.

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Authors and Affiliations

  1. Department of Legal Medicine, Shimane University Faculty of Medicine, 89-1 Enya, Izumo , Shimane, 693-8501, Japan

    Junko Fujihara

  2. Department of Research Planning and Coordination, Shimane Institute for Industrial Technology, 1 Hokuryo, Matsue, Shimane, 690-0816, Japan

    Naoki Nishimoto

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  1. Junko Fujihara
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  2. Naoki Nishimoto
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JF: Writing – original draft, review and editing, visualization. NN: Writing – review and editing, and visualization.

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Correspondence to Junko Fujihara.

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Fujihara, J., Nishimoto, N. Review of Zinc Oxide Nanoparticles: Toxicokinetics, Tissue Distribution for Various Exposure Routes, Toxicological Effects, Toxicity Mechanism in Mammals, and an Approach for Toxicity Reduction. Biol Trace Elem Res 202, 9–23 (2024). https://doi.org/10.1007/s12011-023-03644-w

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