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

Yu, Kyeong-Nam; Yoon, Tae‐Jong; Minai-Tehrani, Arash; Kim, Jieun; Park, Soo‐Jin; Jeong, Min Sook; Ha, Shin-Woo; Lee, Jin-Kyu; Kim, Jun Sung; Cho, Myung‐Haing

doi:10.1016/j.tiv.2013.02.010

Cited by 229 publications

(155 citation statements)

References 40 publications

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“…When the oxidative stress exceeds the antioxidant ability of the cell, oxidative damage on critical biomolecules occurs, leading to cell death. [52][53][54] Importantly, in this study we have demonstrated that ROS are one of the direct causes of ZnO NP-mediated cell death in both in vitro and in vivo models.…”

mentioning

confidence: 56%

Zinc oxide nanoparticles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and <em>Drosophila melanogaster</em>

Yong

Hande³

et al. 2017

IJN

199

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Background Although zinc oxide nanoparticles (ZnO NPs) have been widely used, there has been an increasing number of reports on the toxicity of ZnO NPs. However, study on the underlying mechanisms under in vivo conditions is insufficient. Methods In this study, we investigated the toxicological profiles of ZnO NPs in MRC5 human lung fibroblasts in vitro and in an in vivo model using the fruit fly Drosophila melanogaster . A comprehensive study was conducted to evaluate the uptake, cytotoxicity, reactive oxygen species (ROS) formation, gene expression profiling and genotoxicity induced by ZnO NPs. Results For in vitro toxicity, the results showed that there was a significant release of extracellular lactate dehydrogenase and decreased cell viability in ZnO NP-treated MRC5 lung cells, indicating cellular damage and cytotoxicity. Generation of ROS was observed to be related to significant expression of DNA Damage Inducible Transcript ( DDIT3 ) and endoplasmic reticulum (ER) to nucleus signaling 1 ( ERN1 ) genes, which are ER stress-related genes. Oxidative stress induced DNA damage was further verified by a significant release of DNA oxidation product, 8-hydroxydeoxyguanosine (8-OHdG), as well as by the Comet assay. For the in vivo study using the fruit fly D. melanogaster as a model, significant toxicity was observed in F1 progenies upon ingestion of ZnO NPs. ZnO NPs induced significant decrease in the egg-to-adult viability of the flies. We further showed that the decreased viability is closely associated with ROS induction by ZnO NPs. Removal of one copy of the D. melanogaster Nrf2 alleles further decreased the ZnO NPs-induced lethality due to increased production of ROS, indicating that nuclear factor E2-related factor 2 (Nrf2) plays important role in ZnO NPs-mediated ROS production. Conclusion The present study suggests that ZnO NPs induced significant oxidative stress-related cytotoxicity and genotoxicity in human lung fibroblasts in vitro and in D. melanogaster in vivo. More extensive studies would be needed to verify the safety issues related to increased usage of ZnO NPs by consumers.

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mentioning

confidence: 56%

Zinc oxide nanoparticles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and <em>Drosophila melanogaster</em>

Yong

Hande³

et al. 2017

IJN

199

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“…Also, Yu et al (2009) showed that rare element NPs including samar-ium/europium and gadolinium/terbium, induce serious autophagy in human liver cells [39]. Yu et al (2013) showed that ZNP could induce autophagy in normal skin cells [40].…”

Section: Discussionmentioning

confidence: 99%

The effect of zinc oxide nanoparticles on mouse spermatogenesis

Talebi

Khorsandi

Moridian³

2013

J Assist Reprod Genet

123

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Objective To evaluate the effects of zinc oxide nanoparticles on mouse spermatogenesis. Methods Thirty two adult male NMRI mice were used. Experimental Groups (ZNP-1-ZNP-3) received one of the following treatments daily for 35 days: 5, 50 and 300 mg/kg zinc oxide nanoparticles respectively. Control group received only distilled water. Epididymal sperm parameters, testicular histopathology, morphometric analysis and spermatogenesis assessments were performed for evaluation of the zinc oxide nanoparticles effects on testis. Results Epididymal sperm parameters including sperm number, motility and percentage of abnormality were significantly changed in 50 and 300 mg/kg zinc oxide nanoparticles treated mice (p<0.01). Histopathological criteria such as epithelial vacuolization, sloughing of germ and detachment were significantly increased in 50 and 300 mg/kg zinc oxide nanoparticles treated mice (p<0.001). 300 mg/kg zinc oxide nanoparticles induced formation of multinucleated giant cells in the germinal epithelium. 50 and 300 mg/kg zinc oxide nanoparticles also caused a significant decrease in seminiferous tubule diameter, seminiferous epithelium height and maturation arrest (p<0.001). Conclusion Zinc oxide nanoparticles act as testicular toxicant and further studies are needed to establish its mechanism of action upon spermatogenesis.

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“…As the latter is one of the main sites for ROS generation, any perturbation of this electron transport chain can result in increased ROS production. [60][61][62] Oxidative stress and mitochondrial abnormalities have been reported to play a role in numerous neuropsychiatric disorders. 63,64 TiO 2 NPs were shown to stimulate brain microglia to generate ROS and disturb the mitochondrial energy production.…”

Section: Interaction Of Nps With Mitochondriamentioning

confidence: 99%

Central nervous system toxicity of metallic nanoparticles

Feng¹,

Chen²,

Zhang³

et al. 2015

IJN

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Nanomaterials (NMs) are increasingly used for the therapy, diagnosis, and monitoring of disease- or drug-induced mechanisms in the human biological system. In view of their small size, after certain modifications, NMs have the capacity to bypass or cross the blood–brain barrier. Nanotechnology is particularly advantageous in the field of neurology. Examples may include the utilization of nanoparticle (NP)-based drug carriers to readily cross the blood–brain barrier to treat central nervous system (CNS) diseases, nanoscaffolds for axonal regeneration, nanoelectromechanical systems in neurological operations, and NPs in molecular imaging and CNS imaging. However, NPs can also be potentially hazardous to the CNS in terms of nano-neurotoxicity via several possible mechanisms, such as oxidative stress, autophagy, and lysosome dysfunction, and the activation of certain signaling pathways. In this review, we discuss the dual effect of NMs on the CNS and the mechanisms involved. The limitations of the current research are also discussed.

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

Cited by 229 publications

References 40 publications

Zinc oxide nanoparticles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and <em>Drosophila melanogaster</em>

Zinc oxide nanoparticles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and <em>Drosophila melanogaster</em>

The effect of zinc oxide nanoparticles on mouse spermatogenesis

Central nervous system toxicity of metallic nanoparticles

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