title: Synergistic effects of zinc oxide nanoparticles and Fatty acids on toxicity to caco-2 cells.
abstract: Fatty acids exposure may increase sensitivity of intestinal epithelial cells to cytotoxic effects of zinc oxide (ZnO) nanoparticles (NPs). This study evaluated the synergistic effects of ZnO NPs and palmitic acid (PA) or free fatty acids (FFAs) mixture (oleic/PA 2:1) on toxicity to human colon epithelial (Caco-2) cells. The ZnO NPs exposure concentration dependently induced cytotoxicity to Caco-2 cells showing as reduced proliferation and activity measured by 3 different assays. PA exposure induced cytotoxicity, and coexposure to ZnO NPs and PA showed the largest cytotoxic effects. The presence of FFAs mixture did not affect the ZnO NPs-induced cytotoxicity. Filtration of freshly prepared suspension of NPs through a 0.45-µm pore size membrane significantly reduced the cytotoxicity, indicating a role of concentration or size of particles in cytotoxic effects. The ZnO NPs and PA coexposure induced production of mitochondrial reactive oxygen species (mROS) but not intracellular ROS production, whereas FFAs mixture exposure did not induce mROS and inhibited intracellular ROS. Both ZnO NPs and fatty acids (PA and FFAs mixture) promoted lysosomal destabilization, which was not correlated with cytotoxicity. These results indicated that PA can enhance ZnO NPs-induced cytotoxicity probably by the augmentation of mROS production, whereas FFAs mixture did not affect ROS production. Synergistic effects between ZnO NPs and fatty acids may be important when considering NPs toxicity via oral exposure.
authors.affiliation: Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen, Denmark yica@sund.ku.dk.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Roursgaard
authors.affiliation: Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ali
authors.initials: A
authors.lastname: Kermanizadeh
authors.affiliation: Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Steffen
authors.initials: S
authors.lastname: Loft
authors.affiliation: Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Møller
mesh_terms: D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008247:Lysosomes / Q000187:drug effects; D053768:Metal Nanoparticles / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019301:Oleic Acid / Q000633:toxicity*; D019308:Palmitic Acid / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015034:Zinc Oxide / Q000633:toxicity*
chemical_list: D017382:Reactive Oxygen Species; D019301:Oleic Acid; D019308:Palmitic Acid; D015034:Zinc Oxide
keywords: Caco-2 cells; fatty acid; lysosomal destabilization; mitochondrial ROS; zinc oxide nanoparticle