INSA - Dissertações de mestrado
URI permanente para esta coleção:
Navegar
Percorrer INSA - Dissertações de mestrado por assunto "Bisfenóis (BPs)"
A mostrar 1 - 1 de 1
Resultados por página
Opções de ordenação
- Assessing the pro inflammatory effects of bisphenol compounds using exposure relevant in vitro co culture modelsPublication . Pereira, Gonçalo Alexandre Candeia; Jordan, Peter; Rodrigues, CecíliaInflammation has reached epidemic proportions in industrialized countries, mainly due to unhealthy habits, poor diet, environmental pollution and other factors not yet understood. If uncontrolled or prolonged, inflammation can become chronic and contribute to the development of a number of human diseases, including autoimmune diseases, intestinal diseases and, in the worst cases, tumorigenesis and tumor progression. Exposure to endocrine disrupting chemicals (EDCs) is one environmental factor contributing to inflammation, and recent studies have brought the bisphenol (BP) group of EDCs into the scientific spotlight. They have been strongly linked to various pathologies, including chronic inflammation, and their effect on human gut health is a hot topic in the scientific community. With this in mind, the aim of this work was proposed to analyze the effects of four bisphenols, BPA, BPS-MAE, BPAP and BPP, on intestinal barrier stress and associated pro-inflammatory effects. To achieve this, a co-culture system was optimized and established, consisting of an improved protocol of polarized Caco-2 epithelial cells seeded on PET insert filters in an apical compartment, together with THP-1 derived macrophages in a basolateral compartment. Subsequently, the effects of BPs exposure on barrier integrity, cellular stress and pro-inflammatory cytokine were tested in a wide range of concentrations (from 100 μM to 0.1 μM). Experimentally, we found that the model was capable of delivering BP-specific data on potential health effects. In terms of transepithelial resistance and epithelial stress, we were able to identify some clear trends that need to be consolidated with more independent experimental replicates. In particular, BPA was the least potent inducer of cellular stress responses and changes in epithelial polarization, whereas the BP analogues tested proved to be more disruptive than BPA, with BPP appearing to be the most potentially hazardous, followed by BPAP and then BPS-MAE. To access the inflammation-modulating effects of these compounds, we tested macrophages, either directly or as co-cultured cells, for expression of the pro-inflammatory marker IL-1β using a semiquantitative RT-PCR approach. An important optimization was their priming with IFN-γ to increase the sensitivity of the model and allow for more physiological relevance. Our observations showed that, once again, the BP analogues induced greater effects compared to BPA. BPP appeared to be the more potent inducer of inflammation, followed by BPS-MAE. Both showed elevated levels of the IL-1β marker at all concentrations tested. BPAP and BPA produced more attenuated effects, although significant at higher concentrations. In conclusion, this work has provided us with landmark results on these BPA analogues and their effects on gut health, adding new insights into the 'new generation' of emerging BPs and their potential adverse health effects.