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  • Impact of brominated flame retardants on lipid metabolism: An in vitro approach
    Publication . Maia, Maria Luz; Sousa, Sara; Pestana, Diogo; Faria, Ana; Teixeira, Diana; Delerue-Matos, Cristina; Domingues, Valentina; Calhau, Conceição
    Brominated flame retardants (BFRs) are chemicals employed to lower the flammability of several objects. These endocrine disruptor chemicals are lipophilic and persistent in the environment. Due to these characteristics some have been restricted or banned by the European Union, and replaced by several new chemicals, the novel BFRs (NBFRs). BFRs are widely detected in human samples, such as adipose tissue and some were linked with altered thyroid hormone levels, liver toxicity, diabetes and metabolic syndrome in humans. However, the disturbance in lipid metabolism caused by BFRs with emphases to NBFRs remains poorly understood. In this study, we used a pre-adipocyte (3T3-L1) cell line and a hepatocyte (HepG2) cell line to investigate the possible lipid metabolism disruption caused by four BFRs: hexabromobenzene (HBB), pentabromotoluene (PBT), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB) and hexabromocyclododecane (HBCD). For that purpose, proliferation and Oil Red O assays, as well as, medium fatty acids profile evaluation using Gas chromatography and RNA extraction for quantitative RT-PCR assays were performed. We detected a significant reduction in the proliferation of preadipocytes and an increased lipid accumulation during differentiation caused by HBB. This BFR also lead to a significant increased expression of IL-1β and decreased expression of PGC-1α and adiponectin. Nevertheless, PBT, TBB and HBCD show to increase lipid accumulation in hepatocytes. PBT also display a significant increase of PPARγ gene expression. Lipid accumulation in the cells can occur by diverse mechanisms depending on the BFR. These results highlight the importance of endocrine disruptor compounds in obesity etiopathogeny.
  • Bioactive Lipids of Seaweeds from the Portuguese North Coast: Health Benefits versus Potential Contamination
    Publication . Soares, Cristina; Sousa, Sara; Machado, Susana; Vieira, Elsa; Carvalho, Ana P.; Ramalhosa, Maria João; Morais, Simone; Correia, Manuela; Oliva-Teles, MT; Domingues, Valentina; Delerue-Matos, Cristina
    The total lipid content and lipidic profile of seaweeds harvested in the North Coast and purchased in Portugal were determined in this paper. The amount of total lipids in the different species of seaweeds varied between 0.7 ± 0.1% (Chondrus crispus) and 3.8 ± 0.6% (Ulva spp.). Regarding the fatty acid content, polyunsaturated fatty acids (PUFA) ranged between 0–35%, with Ulva spp. presenting the highest amount; monounsaturated fatty acids (MUFA) varied between 19 and 67%; and saturated fatty acids (SFA) were predominant in C. crispus (45–78%) and Gracilaria spp. (36–79%). Concerning the nutritional indices, the atherogenicity index (AI) was between 0.4–3.2, the thrombogenicity index (TI) ranged from 0.04 to 1.95, except for Gracilaria spp., which had a TI of 7.6, and the hypocholesterolemic/hypercholesterolemic ratio (HH) values ranged between 0.88–4.21, except for Gracilaria spp., which exhibited values between 0.22–9.26. The n6/n3 ratio was below 1 for most of the species evaluated, except for Ascophyllum nodosum, which presented a higher value, although below 2. Considering the PUFA/SFA ratio, seaweeds presented values between 0.11–1.02. The polycyclic aromatic hydrocarbons (PAHs) and aliphatic hydrocarbons (AHCs) contamination of seaweeds under study was also quantified, the values found being much lower than the maximum levels recommended for foodstuff.
  • Brominated flame retardants effect in MCF-7 cells: Impact on vitamin D pathway
    Publication . Sousa, Sara; Maia, Maria Luz; Pestana, Diogo; Teixeira, Diana; Ângelo-Dias, Miguel; Martins, Catarina; Borrego, Luís Miguel; Delerue-Matos, Cristina; Calhau, Conceição; Domingues, Valentina; Faria, Ana
    Brominated flame retardants (BFRs) are persistent environmental pollutants, allowing a constant human exposure which carries several health risks, including the occurrence of breast cancer and vitamin D deficiency. Vitamin D inhibits cell growth and is negatively associated with breast cancer risk. The effect of BFRs in breast cancer and vitamin D pathway is still poorly understood. MCF-7 cells were treated with hexabromocyclododecane (HBCD), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB), hexabromobenzene (HBB) and pentabromotoluene (PBT) using short and long-term exposure protocols. Viability, proliferation, migration, cell cycle and gene expression were assessed. Gene expression of hVDBP and hCYP2R1 was also evaluated in hepatocytes. Long-term exposure of MCF-7 cells to HBB increased cell proliferation and migration, consequently increasing MMP-9 expression. The vitamin D pathway was also altered by BFRs: cells appeared less prepared to activate and transport vitamin D and the signaling, action and inactivation mechanisms were diminished in the presence of BFRs. Untreated MCF-7 cells showed cell cycle arrest in phase G0/G1 in the presence of activated vitamin D. However, when MCF-7 cells were exposed to BFRs, cell cycle was arrested in phase G2/M, possibly due to DNA damage. Nonetheless, calcitriol seems to be able to mitigate the effect of some BFRs exposure, e.g. PBT