Browsing by Issue Date, starting with "2021-02-03"
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- Cellular Mechanisms of Toxicity of Ingested NanomaterialsPublication . Vieira, Adriana Isabel Ramos; Louro, Maria Henriqueta; Silva, Maria JoãoTitanium dioxide (TiO2) nanomaterials (NMs) are used in a variety of consumer products, namely in the food sector, but their application has raised some concerns regarding their negative impacts on human health and particularly, on the gastrointestinal tract (GIT) following digestion, as this may be a major route of exposure. However, the toxicity studies currently available in the literature are contradictory and the majority do not consider the influence of human digestion in the ingested NMs safety assessment. This work aimed to understand the potential toxic effects of three TiO2 NMs (NM-102, NM-103 and NM-105) with distinct physicochemical properties, in the intestine, using human intestinal cells (Caco-2 and HT29-MTX-E12) as in vitro models. It was also intended to comprehend the impact of an in vitro simulated human digestion process on the NMs’ characteristics and to correlate these differences with the toxicity induced by digested TiO2 NMs, in comparison with undigested NMs. Regarding the cytotoxicity, both undigested and digested NM-105 led to a decrease in HT29-MTX-E12 cell viability, which was more pronounced in the digested sample, concomitantly with a decrease in its hydrodynamic size. Furthermore, digested NM-105 induced an increase in the DNA strand break level in both cell lines and in oxidative DNA damage, only in HT29-MTX-E12 cells, thus being classified as potentially genotoxic, through the comet assay. Digested NM-103 showed also an equivocal genotoxic response in Caco-2 cells. FPG-modified comet assay revealed an induction of DNA oxidative base lesions in Caco-2 and HT29-MTX-E12 exposed to undigested NM-103 and NM-102. Lastly, through the micronucleus assay, increased chromosomal damage effects were observed following treatment with some of the undigested and digested NMs. The present results reinforce the conception that NMs biological interactions are context-dependent, since their physicochemical properties can be changed after the digestion process, consequently leading to different biological effects.
- Exposure to Xenobiotics and Gene-Environment Interactions in Autism Spectrum Disorder: A Systematic Review [CHAPTER 7]Publication . Xavier Santos, João; Rasga, Célia; Moura Vicente, AstridHeritability estimates indicate that genetic susceptibility does not fully explain Autism Spectrum Disorder (ASD) risk variance, and that environmental factors may play a role in this disease. To explore the impact of the environment in ASD etiology, we performed a systematic review of the literature on xenobiotics implicated in the disease, and their interactions with gene variants. We compiled 72 studies reporting associations between ASD and xenobiotic exposure, including air pollutants, persistent and non-persistent organic pollutants, heavy metals, pesticides, pharmaceutical drugs and nutrients. Additionally, 9 studies reported that interactions between some of these chemicals (eg. NO2, particulate matter, manganese, folic acid and vitamin D) and genetic risk factors (eg. variants in the CYP2R1, GSTM1, GSTP1, MET, MTHFR and VDR genes) modulate ASD risk. The chemicals highlighted in this review induce neuropathological mechanisms previously implicated in ASD, including oxidative stress and hypoxia, dysregulation of signaling pathways and endocrine disruption. Exposure to xenobiotics may be harmful during critical windows of neurodevelopment, particularly for individuals with variants in genes involved in xenobiotic metabolization or in widespread signaling pathways. We emphasize the importance of leveraging multilevel data collections and integrative approaches grounded on artificial intelligence to address gene–environment interactions and understand ASD etiology, towards prevention and treatment strategies.