Chronic effects of two rutile TiO2 nanomaterials in human intestinal and hepatic cell lines

Abstract

Background TiO2 nanomaterials (NMs) are present in a variety of food and personal hygiene products, and consumers are exposed daily to these NMs through oral exposition. While the bulk of ingested TiO2 NMs are eliminated rapidly in stool, a fraction is able to cross the intestinal epithelial barrier and enter systemic circulation from where NMs can be distributed to tissues, primarily liver and spleen. Daily exposure to TiO2 NMs, in combination with a slow rate of elimination from tissues, results in their accumulation within different tissues. Considerable evidence suggests that following oral exposure to TiO2 NMs, the presence of NMs in tissues is associated with a number of adverse effects, both in intestine and liver. Although numerous studies have been performed in vitro investigating the acute effects of TiO2 NMs in intestinal and hepatic cell models, considerably less is known about the effect of repeated exposure on these models. In this study, we investigated the cytotoxic effects of repeated exposure of relevant models of intestine and liver to two TiO2 NMs differing in hydrophobicity for 24 h, 1 week and 2 weeks at concentrations ranging from 0.3 to 80 µg/cm2. To study the persistence of these two NMs in cells, we included a 1-week recovery period following 24 h and 1-week treatments. Cellular uptake by TEM and ToF–SIMS analyses, as well as the viability and pro-inflammatory response were evaluated. Changes in the membrane composition in Caco-2 and HepaRG cells treated with TiO2 NMs for up to 2 weeks were also studied. Results Despite the uptake of NM-103 and NM-104 in cells, no significant cytotoxic effects were observed in either Caco-2 or HepaRG cells treated for up to 2 weeks at NM concentrations up to 80 µg/cm2. In addition, no significant effects on IL-8 secretion were observed. However, significant changes in membrane composition were observed in both cell lines. Interestingly, while most of these phospholipid modifications were reversed following a 1-week recovery, others were not affected by the recovery period. Conclusion These findings indicate that although no clear effects on cytotoxicity were observed following repeated exposure of differentiated Caco-2 and HepaRG cells to TiO2 NMs, subtle effects on membrane composition could induce potential adverse effects in the long-term.

DNA Oxidative Damage as a Sensitive Genetic Endpoint to Detect the Genotoxicity Induced by Titanium Dioxide Nanoparticles

“…Cytotoxicity was determined by the physicochemical properties, exposure concentration and time of nanoparticles [ 23 , 41 ]. Coarse particles of titanium dioxide or nanoparticles exposed to low doses for long-term exposure have also shown low cytotoxicity [ 42 , 43 ]. The mechanism of cytotoxicity may be related to oxidative stress, inflammatory response and genotoxicity induced by TiO 2 NPs [ 29 , 44 ].…”

Microbial synthesis of titanium dioxide nanoparticles and their importance in wastewater treatment and antimicrobial activities: a review

“…When the TiO 2 NPs are exposed to UV light, the electrons in the valence band get excited and reach the CB. Consequently, there is a formation of electrons (e CB− ) and VB holes (h + VB ) (Khalafi et al, 2019) Silva et al, 2017;Amano et al, 2022;Jalili et al, 2022;Sudrajat et al, 2022;Yang F. et al, 2022 the TiO 2 NPs. Furthermore, there is an interaction between these photo-excited e −s and O 2 dissolved in the liquid medium, which contains pollutants such as dyes and pesticides.…”

Adverse Outcome Pathways Associated with the Ingestion of Titanium Dioxide Nanoparticles—A Systematic Review

“…Some of the collected reports describe a lack of toxicity after TiO 2 exposure in spite of its uptake and translocation through the cells without disrupting junctional complexes or epithelial integrity [31,44,110,118]. A very recent study showed that, although no clear effects on cytotoxicity were observed following repeated exposure of differentiated Caco-2 and HepaRG cells to TiO 2 -NPs, subtle effects on membrane composition could induce potential adverse effects in the long-term [127]. On the other hand, there are results supporting that the toxicity attributed to TiO 2 is related with its cellular accumulation, which may potentially lead to the dysregulation of cell function and cell death [37,47,51,120].…”