Exposure to ZnO nanoparticles induces oxidative stress and cytotoxicity in human colon carcinoma cells.
Engineered nanoparticles offer great promise in many industrial and biomedical applications, however little information is available about gastrointestinal toxicity. The purpose of this study was to assess the cytotoxicity, oxidative stress, apoptosis and proinflammatory mediator release induced by ZnO nanoparticles on human colon carcinoma LoVo cells. The biological activity of these particles was related to their physico-chemical characteristics. The physico-chemical characteristics were evaluated by analytical electron microscopy. The cytotoxicity was determined by growth curves and water-soluble tetrazolium assay. The reactive oxygen species production, cellular glutathione content, changes of mitochondrial membrane potential and apoptosis cell death were quantified by flow cytometry. The inflammatory cytokines were evaluated by enzyme-linked immunoadsorbent assay. Treatment with ZnO (5μg/cm(2) corresponding to 11.5μg/ml) for 24h induced on LoVo cells a significant decrease of cell viability, H2O2/OH increase, O2(-) and GSH decrease, depolarization of inner mitochondrial membranes, apoptosis and IL-8 release. Higher doses induced about 98% of cytotoxicity already after 24h of treatment. The experimental data show that oxidative stress may be a key route in inducing the cytotoxicity of ZnO nanoparticles in colon carcinoma cells. Moreover, the study of the relationship between toxicological effects and physico-chemical characteristics of particles suggests that surface area does not play a primary role in the cytotoxicity.
De Berardis
Barbara
B
Department of Technology and Health, Italian National Institute of Health, Viale Regina Elena 299, 00161 Rome, Italy.
Civitelli
Gabriele
G
Condello
Maria
M
Lista
Pasquale
P
Pozzi
Roberta
R
Arancia
Giuseppe
G
Meschini
Stefania
S
D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053758:Nanoparticles / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014025:Titanium / Q000494:pharmacology; D015034:Zinc Oxide / Q000494:pharmacology*
D016209:Interleukin-8; D017382:Reactive Oxygen Species; C009495:titanium dioxide; D006861:Hydrogen Peroxide; D014025:Titanium; D005978:Glutathione; D015034:Zinc Oxide