TY - JOUR

T1 - Synergistic effects of zinc oxide nanoparticles and Fatty acids on toxicity to caco-2 cells

AU - Cao, Yi

AU - Roursgaard, Martin

AU - Kermanizadeh, Ali

AU - Loft, Steffen

AU - Møller, Peter

N1 - © The Author(s) 2014.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

KW - Caco-2 Cells

KW - Cell Survival/drug effects

KW - Humans

KW - Lysosomes/drug effects

KW - Metal Nanoparticles/toxicity

KW - Mitochondria/drug effects

KW - Oleic Acid/toxicity

KW - Palmitic Acid/toxicity

KW - Reactive Oxygen Species/metabolism

KW - Zinc Oxide/toxicity

U2 - 10.1177/1091581814560032

DO - 10.1177/1091581814560032

M3 - Article

C2 - 25421740

VL - 34

SP - 67

EP - 76

JO - Archives of toxicology

JF - Archives of toxicology

SN - 0340-5761

IS - 1

ER -