title: Toxicity of zinc oxide (ZnO) nanoparticles on human bronchial epithelial cells (BEAS-2B) is accentuated by oxidative stress.
abstract: Although several studies reported that cytotoxic effects of various nanoparticles are partially due to induction of oxidative stress, it is unclear how oxidative state of the cell per se could influence its sensitivity to cytotoxic nanoparticles. This is of clinical significance because certain pathological conditions such as inflammation is associated with elevated oxidative stress and this may alter sensitivity of cells and tissues to cytotoxic nanoparticles. Hence, this study investigated how initial exposure of BEAS-2B human bronchial epithelial cells to oxidative stress influences subsequent response to cytotoxic challenge with zinc oxide (ZnO) nanoparticles (approximately 10nm). Oxidative stress was induced by exposing BEAS-2B cells to 5 and 10 microM of H(2)O(2) for 45 min in PBS (with Ca(2+)). Subsequently, the H(2)O(2) solutions were washed off and the cells were exposed to varying concentrations (5-25 microg/ml) of ZnO nanoparticles in culture media for 24h, followed by cell viability assessment with the WST-8 assay. The results demonstrated that initial transient exposure of cells to oxidative stress accentuated cytotoxicity of ZnO nanoparticles. In the negative control unexposed to H(2)O(2), >99% of cells remained viable up to a ZnO nanoparticle concentration of 10 microg/ml, but displayed a steep decrease in viability above 10 microg/ml ZnO. By contrast, cells that were initially exposed to 5 and 10 microM of H(2)O(2), displayed a sharp drop in viability even at concentrations below 10 microg/ml ZnO. At 10 microg/ml ZnO, cells initially exposed to 10 microM H(2)O(2) displayed a viability of 40.6+/-2.0%, which is significantly lower than the corresponding values of 72.8+/-2.0% and 99.9+/-1.1% obtained for initial exposure to 5 microM H(2)O(2) and the negative control, respectively. Hence, initial exposure of BEAS-2B cells to oxidative stress sensitized their subsequent response to cytotoxic challenge with ZnO nanoparticles.
authors.affiliation: School of Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore. Alexishengbc@ntu.edu.sg
authors.forename: Boon Chin
authors.initials: BC
authors.lastname: Heng
authors.forename: Xinxin
authors.initials: X
authors.lastname: Zhao
authors.forename: Sijing
authors.initials: S
authors.lastname: Xiong
authors.forename: Kee Woei
authors.initials: KW
authors.lastname: Ng
authors.forename: Freddy Yin-Chiang
authors.initials: FY
authors.lastname: Boey
authors.forename: Joachim Say-Chye
authors.initials: JS
authors.lastname: Loo
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053768:Metal Nanoparticles; D015034:Zinc Oxide / Q000633:toxicity*
chemical_list: D015034:Zinc Oxide