Zinc oxide nanoparticle induced autophagic cell death and mitochondrial damage via reactive oxygen species generation

• Published in: Toxicology in vitro 2013-06, Vol.27 (4), p.1187-1195
• Main Authors: Yu, Kyeong-Nam, Yoon, Tae-Jong, Minai-Tehrani, Arash, Kim, Ji-Eun, Park, Soo Jin, Jeong, Min Sook, Ha, Shin-Woo, Lee, Jin-Kyu, Kim, Jun Sung, Cho, Myung-Haing
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Animals; Autophagy; Autophagy - drug effects; Cell Line; Cytotoxicity; Membrane Potential, Mitochondrial - drug effects; Metal Nanoparticles - toxicity; Metal Nanoparticles - ultrastructure; Mice; Microscopy, Electron, Transmission; Mitochondria - drug effects; Mitochondria - physiology; Mitochondria damage; Reactive oxygen species (ROS); Reactive Oxygen Species - metabolism; Zinc Oxide - toxicity; Zinc oxide nanoparticles
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2013.02.010

► Potential toxicity and mechanism of ZnO-np were assessed in normal skin cells. ► ZnO-np induces ROS generation in normal skin cells. ► ZnO-np induces autophagy accumulation and leads to cell death. ► ZnO-np affects to mitochondria disruption and dysfunction. 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.