Cytotoxic and proinflammatory responses induced by ZnO nanoparticles in in vitro intestinal barrier

Abstract

ZnO nanoparticles (NPs) are widely used nowadays, thus the gastrointestinal exposure to ZnO NPs is likely to be relevant and the effects on the intestinal barrier should be investigated. Polarized Caco-2 cells were exposed from the apical (Ap) and basolateral (Bl) compartments to increasing concentrations (0, 10, 50 and 100 μg/mL) of sonochemical (sono) and commercial ZnO NPs. The transepithelial electrical resistance (TEER), cell viability, proinflammatory cytokine release and presence of protein oxidative damage were evaluated after exposure. TEER was not significantly affected by Ap exposure to either sono or commercial ZnO NPs at any tested concentrations. After Bl exposure to sono ZnO NPs (all the concentrations) and to 100 μg/mL of commercial ZnO NPs TEER was decreased (P < 0.05). Ap and Bl exposure to 100 μg/mL sono ZnO NPs and Ap exposure to 50 μg/mL commercial ZnO NPs induced a significant (P < 0.05) release of interleukin-6. A significant (P < 0.05) release of interleukin-8 was observed after Ap exposure to ZnO NPs at 100 μg/mL and after Bl exposure to sono ZnO NPs at 100 μg/mL. Ap or Bl exposure to sono or commercial ZnO NPs did not affect tumour necrosis factor-alpha secretion or protein sulphydryl oxidation. In conclusion, the ZnO NP exposure from the Ap compartment appeared almost safe, while the exposure through the basal compartment appeared to be more hazardous and the different NP size and crystallinity seem to affect the mode of action, but further studies are necessary to elucidate better these toxicity mechanisms.

Changes of physico-chemical properties of nano-biomaterials by digestion fluids affect the physiological properties of epithelial intestinal cells and barrier models

“…This balance, together with the over-expression of TJ genes, likely contributes to prevent barrier damage and integrity loss. Our data are in line with the work of Colombo and co-workers, reporting that commercial ZnO nanoparticles increase IL-6 and IL-8 production in Caco-2 barrier model, maintaining barrier integrity [ 127 ]. Similarly, polyvinyl chloride particles have been reported to induce IL-1β secretion without altering Caco-2/HT29-MTX/THP1 barrier integrity and viability [ 128 ].…”

On the In Vitro and In Vivo Hazard Assessment of a Novel Nanomaterial to Reduce the Use of Zinc Oxide in the Rubber Vulcanization Process

“…Low toxicity and low inflammatory profile of novel NMs are essential for their safety. The concentrations of ZnO NPs generally used in the literature are within the range of 25 to 100 µg/mL, and the effects reported in vitro almost suggest safety for this NP [41]. The same is reported for toxicity of SiO 2 NPs that occurs to be dependent on dose, size, time, and temperature in addition to on the tissue-specificity.…”

“…Organic and inorganic nanoparticles (NPs) Adult Stem Cells (ASCs) [50] Iron oxide nanoparticles (IONPs) Primary cultures of brain cells [51] Various types of nanoparticles Cardiac stem cells [52] Gold nanoparticles breast cancer SK-BR-3 cells [53] titanium dioxide (TiO 2 ) nanoparticles A549 cells [54] ZnO nanoparticles Caco-2 cells [41] biosynthesized silver nanoparticles (ScAgNPs) THP-1 cells [55] Cerium dioxide nanoparticles (CeO 2 NPs) A549 cells and THP-1 cells (co-culture) [56] Silver (Ag), titanium dioxide (TiO 2 ), and zinc oxide (ZnO) nanoparticles THP-1 cells [57] Tantalum (Ta) and Titanium (TiO 2 ) NPs THP-1 cells [58] Silver nanoparticle (AgNP) THP-1 cells [59] Polystyrene NP (PLNP) A549 cells and THP-1 cells [60] Amino-functionalized silicon nanoparticle (NH2SiNP) MC3T3-E1 and PC12 cells and Danio rerio (embryos) [61] Iron nanoparticles Xenopus laevis (embryos) [62] Titanium dioxide NPs (n-TiO(2)) Danio rerio (embryos) [63] Silicon dioxide nanoparticles (nano-SiO(2)) Danio rerio (embryos) [64] Ag nanoparticles (NPs), CuO NPs, silica NPs, polymeric NPs, quantum dots Danio rerio (embryos) [65] Zirconia oxide nanoparticles (ZrO 2 NPs) Danio rerio (embryos) [66] Polyethylene glycol (PEG)-modified SiNPs Danio rerio (embryos) [67] Silver (AgNPs), copper nanoparticles (CuNPs) Danio rerio (embryos) [68] Silver nanoparticles (Ag NPs) of three different sizes (10, 40, and 100 nm) Danio rerio (embryos) [69] Hollow selenium nanoparticles (hSeNPs) Danio rerio (embryos) [70] Copper oxide nanoparticles (CuO NPs) Danio rerio (embryos) [71] Synthetic silver nanoparticles (AgNPs) Danio rerio (embryos) [72] Fluorescently-labeled SiO 2 NPs of 25 and 115 nm Danio rerio (embryos) [73] Citrate-functionalized IONPs (γ-Fe 2 O 3 ) NPs Danio rerio (embryos) [74] Silver nanoparticles (AgNPs) Danio rerio (embryos) [48] Metal nanoparticles (Au, Ag, Cu), and metal oxide nanoparticles (TiO 2 , Al 2 O 3 , CuO, NiO, ZnO) Danio rerio (embryos) [75] Zinc oxide nanoparticles (ZnONPs) Danio rerio (embryos) [76] Sliver nanop...…”

Impact of in vitro digested zinc oxide nanoparticles on intestinal model systems

“…Some studies identified negative biological consequences, for example an increased intestinal inflammation, decreased cell viability and depolarization of mitochondrial membranes, induced by the ZnO NP treatment [ 11 , 12 ]. Others showed rather inconclusive results that could not demonstrate ZnO NP toxicity in some assays, for instance an unmodified monolayer permeability but a disrupted brush border membrane [ 13 – 17 ], or concluded the innocuousness of a ZnO NP exposure [ 18 – 23 ]. The toxicity seems to depend on the used cell model, among other factors [ 24 ].…”