Zinc Oxide Nanoparticle Induced Autophagic Cell Death and Mitochondrial Damage via Reactive Oxygen Species Generation
Abstract
Zinc oxide nanoparticles (ZnO-np) are used in an increasing number of industrial products such as paint, coating and cosmetics, and in other biological applications. There have been many suggestions of a ZnO-np toxicity paradigm but the underlying molecular mechanisms about the toxicity of ZnO-np remain unclear. This study was done to determine the potential toxicity of ZnO-np and to assess the toxicity mechanism in normal skin cells. Synthesized ZnO-np generated reactive oxygen species (ROS), as determined by electron spin resonance. After uptake into cells, ZnO-np induced ROS in a concentration- and time-dependent manner. To demonstrate ZnO-np toxicity mechanism related to ROS, we detected abnormal autophagic vacuoles accumulation and mitochondria dysfunction after ZnO-np treatment. Furthermore mitochondria membrane potential and adenosine-5'-triphosphate (ATP) production are decreased for culture with ZnO-np. We conclude that ZnO-np leads to cell death through autophagic vacuole accumulation and mitochondria damage in normal skin cells via ROS induction. Accordingly, ZnO-np may cause toxicity and the results highlight and need for careful regulation of ZnO-np production and use.
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Zinc overload can contribute to increased cellular oxidative stress and senescence through mechanisms possibly related to organelle dysfunction.
“On the other hand, Zn overload can contribute to augment cellular OS and senescence through different mechanisms not yet well-defined, but possibly related to organelles dysfunction [411,427,438].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [427]
Zinc deficiency causes destabilization of membrane structure and increases oxidative stress.
“In this respect, evidence showed that Zn deficiency causes destabilization of membrane structure and augments OS [424,425,426,427,428].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [427]
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- Authors
- Yu, K.-N., Yoon, T.-J., Minai-Tehrani, A., Kim, J.-E., Park, S. J., Jeong, M. S., Ha, S.-W., Lee, J.-K., Kim, J. S., & Cho, M.-H.
- Affiliations
- Seoul National University (KR)
- CHA University (KR)
- Emory University (US)
- Corresponding author
- Kim, Jun Sung
- Cho, Myung-Haing
- Venue
- Toxicology in Vitro
- Publisher
- Elsevier BV
- Published
- 2013-06
- Volume
- 27
- Issue
- 4
- Pages
- 1187-1195
- ISSN
- 0887-2333 (ISSN-L)
- OpenAlex
- W1966626824
- Cited by
- 268
- References
- 43
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 15 · 2023: 16 · 2022: 17 · 2021: 20 · 2020: 28 · 2019: 31 · 2018: 26 · 2017: 16 · 2016: 26 · 2015: 25 · 2014: 21 · 2013: 5
- FWCI
- 11.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology in Vitro (publishedVersion)
- PubMed (publishedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University
- National Research Foundation of Korea
- Ministry of Education, Science and Technology (2009-0082737, 2010-0019991, 2011-0019175)
- Topics
- Physical Sciences › Materials Science › Materials Chemistry › Nanoparticles: synthesis and applications
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
- Keywords
- zinc oxide nanoparticles, nanoparticle toxicity, autophagic cell death, mitochondrial damage, mitochondrial dysfunction, reactive oxygen species, mitochondrial membrane potential, ATP production, skin cells, nanoparticle uptake
- MeSH terms
- Adenosine Triphosphate, Animals, Autophagy, Cell Line, Mitochondria, Zinc Oxide, Reactive Oxygen Species, Microscopy, Electron, Transmission, Mice, Membrane Potential, Mitochondrial, Metal Nanoparticles
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