Biodisponibilitat i efectes dels micro i nanoplàstics en models gastrointestinals in vitro. Un focus en el nanopolistirè com a material plàstic representatiu de mida nanomètrica
- Autores: Josefa Domenech Cabrera
- Directores de la Tesis: Constanza Lorena Cortés Crignola (dir. tes.), Alba Hernández Bonilla (codir. tes.), Ricardo Marcos Dauder (codir. tes.)
- Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2021
- Idioma: catalán
- Tribunal Calificador de la Tesis: M. Antonia Velázquez Henar (presid.), Antonio Guzmán Cano (secret.), Alba García Rodriguez (voc.)
- Programa de doctorado: Programa de Doctorado en Genética por la Universidad Autónoma de Barcelona
- Materias:
- Enlaces
- Tesis en acceso abierto en: TDX
- Resumen
Owing to the wide range of tuneable physicochemical properties, and the rapid and low-cost production, plastics present uncountable applications in industry such as product packaging, agriculture, medical applications, building or electronics, among others. This fact leads to the corresponding exponential increase in the generated plastic waste that ends up contaminating the environment. Different environmental conditions favour physical, chemical and biological processes that drive plastic waste to a continuous degradation, generating the so-called micro- and nanoplastics (MNPLs). In addition to those, rapid advances in nanotechnology have driven to the target industrial production of plastic particles in the micro- and nano-size ranges used in cosmetic or cleaning products that contribute to plastic environmental pollution.
The increasing presence of MNPLs in nature represents an environmental challenge but this is also accompanied by the human exposure. Nevertheless, the current methodological limitations do not allow for accurate estimations on the levels of human exposure, and the scarcity of data on the effects of MNPLs in mammalian models hampers the understanding of whether the presence of MNPLs in different environmental niches and organisms may pose a risk for humans. Aiming to contribute to expand the knowledge on human exposure and the potential toxic and genotoxic effects of MNPLs on human health, we have reviewed the last publications referring to the occurrence of MNPLs in food and airborne, and we have performed extended in vitro studies on the biological effects of polystyrene nanoparticles (PSNPs).
Our review of literature revealed ingestion as the major human exposure route to MNPLs and highlighted the knowledge gaps and limitations conditioning the MNPLs hazard assessment. Therefore, we moved forward to evaluate the interactions of PSNPs with different human gastrointestinal in vitro models, as well as toxicity and genotoxicity of the nanoplastics in those models. We confirmed the ability of PSNPs to internalise into human-derived undifferentiated Caco-2 cells. Importantly, Caco-2 cells showed signals of general stress induction after the exposure to PSNPs. However, although PSNPs reached the cell nuclei in only 24 h, cells did not show genotoxicity.
Because of the heightened interest in the effects of MNPLs after their ingestion, we further analysed, the internalisation ability of PSNPs in Caco-2 based in vitro 2D models of the gut barrier which include representation of goblet (Caco-2/HT29) and microfold-cells (Caco-2/HT29/Raji-B). Our findings describe PSNPs as weak toxicants due to their low ability to induce ROS or other toxic effects. Similar to that found in the undifferentiated Caco-2 model, PSNPs did not exert genotoxic or oxidative DNA damage despite having a great internalisation capacity which allowed reaching cell nuclei and translocation across the barriers.
Although literature regarding MNPLs health effects show controversy, the exposure scenario is aggravated if the MNPLs’ ability as carriers of other hazard contaminants is considered. Therefore, we attempted to cover this aspect by introducing the co-exposure design. Our results demonstrated the physical interaction between PSNPs and a widespread legacy pollutant, silver nanoparticles (AgNPs). Importantly, we proved the adaptability of classical methodological approaches to novel technical challenges as it is the visualisation of the metals/MNPLs interplay. In addition, we observed an enhancement of AgNPs internalisation by undifferentiated Caco-2 cells, after the co-exposure to AgNPs/PSNPs, but not a higher induction of toxic effects after the co-treatment. On the other hand, AgNPs/PSNPs complexes internalised and reached Caco-2 cell nuclei, causing an increasing tendency to genotoxic damage as the AgNPs concentration increases when combined with high doses of PSNPs. Silver nitrate (AgNO3) was included in this study as a surrogate of silver ion releasing agent to confirm that the effects induced by AgNPs were not caused by released ions.
