Low Concentrations of Zinc Oxide Nanoparticles Cause Severe Cytotoxicity Through Increased Intracellular Reactive Oxygen Species

With wide application of Zinc oxide (ZnO) nanoparticles, their biological toxicity has received more and more attention in recent years. In this research, two ZnO dispersions with different particle sizes, small size Zinc oxide (S-ZnO) and big size Zinc oxide (B-ZnO), were prepared using polycarboxylic acid as dispersant. We found that the S-ZnO nanoparticles showed stronger toxicity on Human Pulmonary Alveolar Epithelial Cells (HPAEpiC) under same concentration. Only 9 ppm S-ZnO could decrease HPAEpiC viability to about 50%, which means that, a small amount of well-dispersed ZnO nanoparticles in industrial production process may cause serious damage to the human body through oral inhalation. Focusing on mechanism for cytotoxicity, ZnO nanoparticles promoted generation and accumulation of Reactive Oxygen Species (ROS) in mitochondria via inhibiting Superoxide Dismutase (SOD) enzyme activity and reducing Glutathione (GSH) content. ROS in turn opened the mitochondrial Ca2+ pathway and lowered the Mitochondrial Membrane Potentials (MMP), leading to cell death. To simulate the lung environment in vitro, mixed dipalmitoyl phosphatidylcholine (DPPC) and ZnO nanoparticles (1:1) were incubated for 72 hours and then cytotoxicity was evaluated on HPAEpiC. Results showed that the cell viability was significantly increased, which proved that the DPPC effectively inhibited the toxicity of ZnO nanoparticles.

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N-acetylcysteine protects alveolar epithelial cells from hydrogen peroxide–induced apoptosis through scavenging reactive oxygen species and suppressing c-Jun N-terminalkinase

Experimental Lung Research ◽

10.3109/01902141003678582 ◽

2010 ◽

Vol 36 (6) ◽

pp. 352-361 ◽

Cited By ~ 15

Author(s):

Yue-qiang Fu ◽

Fang Fang ◽

Zhong-yi Lu ◽

Feng-wu Kuang ◽

Feng Xu

Keyword(s):

Reactive Oxygen Species ◽

Hydrogen Peroxide ◽

Epithelial Cells ◽

Reactive Oxygen ◽

Alveolar Epithelial Cells ◽

Oxygen Species ◽

Alveolar Epithelial ◽

Induced Apoptosis

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Neutrophils Kill Reactive Oxygen Species-Resistant Pseudomonas aeruginosa by Sphingosine

Cellular Physiology and Biochemistry ◽

10.1159/000482024 ◽

2017 ◽

Vol 43 (4) ◽

pp. 1603-1616 ◽

Cited By ~ 6

Author(s):

Katrin Anne Becker ◽

Xiang Li ◽

Aaron Seitz ◽

Joerg Steinmann ◽

Anne Koch ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Pseudomonas Aeruginosa ◽

Reactive Oxygen ◽

Early Death ◽

Oxygen Species ◽

New Paradigm ◽

Bacterial Killing ◽

Low Concentrations ◽

Massive Accumulation

Background/Aims: Cystic fibrosis (CF) is dominated by chronic inflammation and infection of the lung resulting in lung destruction and early death of patients. The lungs of CF patients are characterized by a massive accumulation of neutrophils. It requires definition why these massive numbers of neutrophils fail to eliminate typical CF pathogens like Staphylococcus aureus and Pseudomonas aeruginosa (P. aeruginosa) in CF lungs. Methods: We determined ceramide, sphingosine and reactive oxygen species (ROS) in neutrophils from wildtype and CF mice and determined the effect of sphingosine and ROS alone or in combination on killing of different P. aeruginosa strains. Results: We demonstrate that wildtype neutrophils are able to kill non-mucoid and mucoid clinical P. aeruginosa strains, while neutrophils from CF mice are insufficient to kill these P. aeruginosa strains, although both types of neutrophils infected with P. aeruginosa produce comparable levels of superoxide. All three analyzed P. aeruginosa strains are resistant to reactive oxygen species. The inability of CF neutrophils to kill P. aeruginosa is caused by a marked decrease of surface sphingosine levels in CF neutrophils. Wildtype neutrophils contain much higher concentrations of surface sphingosine than CF neutrophils. Further, wildtype neutrophils, but not CF neutrophils, release sphingosine, most likely as microparticles, upon infection. Sphingosine kills P. aeruginosa in vitro at low micromolar concentrations. Reconstitution of sphingosine in CF neutrophils restores their ability to kill these pathogens, demonstrating the significance of sphingosine for bacterial killing. Conclusion: The data provide evidence for a new paradigm explaining how neutrophils kill ROS-resistant P. aeruginosa, i.e. by sphingosine that kills P. aeruginosa at low concentrations. This mechanism is defective in CF neutrophils.

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Mitochondrial DNA-depleted A549 cells are resistant to bleomycin

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00343.2011 ◽

2012 ◽

Vol 303 (5) ◽

pp. L413-L424 ◽

Cited By ~ 22

Author(s):

Sukhdev S. Brar ◽

Joel N. Meyer ◽

Carl D. Bortner ◽

Bennett Van Houten ◽

William J. Martin

Keyword(s):

Reactive Oxygen Species ◽

Dna Damage ◽

Mitochondrial Dna ◽

Molecular Mechanisms ◽

Caspase 3 ◽

A549 Cells ◽

Reactive Oxygen ◽

Alveolar Epithelial Cells ◽

Oxygen Species ◽

Alveolar Epithelial

Alveolar epithelial cells are considered to be the primary target of bleomycin-induced lung injury, leading to interstitial fibrosis. The molecular mechanisms by which bleomycin causes this damage are poorly understood but are suspected to involve generation of reactive oxygen species and DNA damage. We studied the effect of bleomycin on mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) in human alveolar epithelial A549 cells. Bleomycin caused an increase in reactive oxygen species production, DNA damage, and apoptosis in A549 cells; however, bleomycin induced more mtDNA than nDNA damage. DNA damage was associated with activation of caspase-3, cleavage of poly(ADP-ribose) polymerase, and cleavage and activation of protein kinase D1 (PKD1), a newly identified mitochondrial oxidative stress sensor. These effects appear to be mtDNA-dependent, because no caspase-3 or PKD1 activation was observed in mtDNA-depleted (ρ0) A549 cells. Survival rate after bleomycin treatment was higher for A549 ρ0 than A549 cells. These results suggest that A549 ρ0 cells are more resistant to bleomycin toxicity than are parent A549 cells, likely in part due to the depletion of mtDNA and impairment of mitochondria-dependent apoptotic pathways.

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