RESUMEN

In vitro models of the intestinal barrier are being increasingly used to evaluate nanoparticles (NPs) exposure risk. Nevertheless, most of these studies have focused on short-term exposures lasting no more than 24 h of duration, which could underestimate the toxic effects of a given compound under a more realistic setting. Since the assessment of longer exposure time-points is crucial to evaluate the risk of cumulative exposure to NPs, we have analyzed the effects of AgNPs at different exposure time-points between 6 h and 4 days on the barrier model system constituted by Caco-2/HT29 cells. Our results indicate that i) the system is stable during this time frame; ii) AgNPs affect the barrier's integrity only at the highest concentration tested (100 µg/mL), and only after 96 h of exposure; iii) cellular uptake of AgNPs showed a time-dependent and concentration-dependent increase; iv) translocation through the barrier was only observed at the highest concentration and only after 96 h of exposure; v) the expression of genes involved in the barrier's structure differs depending on the exposure time analyzed. All these results reinforce our proposal of expanding exposure times beyond 24 h when performing assays for hazard assessment of NPs using in vitro models of the intestinal barrier.

Asunto(s)

Nanopartículas del Metal/toxicidad , Plata/toxicidad , Células CACO-2 , Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Expresión Génica/efectos de los fármacos , Células HT29 , Humanos , Nanopartículas del Metal/química , Plata/química , Plata/metabolismo , Factores de Tiempo