PPG - Bioprodutos e Bioprocessos

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https://hdl.handle.net/11600/61205

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Navegando PPG - Bioprodutos e Bioprocessos por Orientador(es) "Barcelos, Gustavo Rafael Mazzaron [UNIFESP]"

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    Avaliação da citotoxicidade e genotoxicidade da coexposição ao Triclosan e ao Ftalato DEHP em células HepG2
    (Universidade Federal de São Paulo (UNIFESP), 2021) Lima, Lindiane Eloisa De [UNIFESP]; Barcelos, Gustavo Rafael Mazzaron [UNIFESP]; Universidade Federal de São Paulo
    Triclosan (TCS) is widely used as a preservative and bactericide in personal care products, household items, sports equipment, and toys. Di-2-ethylhexyl phthalate (DEHP) is the main derivative of phtalic acid, can give malleability to plastic, which is why it is widely used in medical devices, toys, building materials, etc. Considered endocrine disrupters and environmental contaminants, studies have shown several adverse effects, however the majority have an emphasis on ecotoxicology using aquatic organisms, thus, there is little data about the evaluation of the possible adverse effects of these contaminants in mammals. This study aims to assess the impact of exposure to TCS, DEHP, as well as their associations, on cell viability and genomic stability, in HepG2 cells. The MTT and Red Neutral (VN) assays were used to assess cytotoxicity using different concentrations of TCS and DEHP (0.3 - 50 µM) and the cells were exposed for 24 hours. From the results of these tests, three concentrations of each toxicant were chosen (0.10; 1.0 and 10 µM), for subsequent monitoring of cell viability and DNA damage, by the comet assay. The results show that the lysosomal pathway was not affected by coexposure to toxicants; however, mitochondrial activity was compromised at all concentrations tested, especially in combinations of the lowest DEHP concentration (0.10 µM) with TCS concentrations 0.10 µM (44%), 1.0 µM (17%) and 10 µM (21%). Genotoxicity by the comet assay showed greater DNA damage at concentrations of 0.10 µM TCS (16.4%) and 1.0 µM DEHP (19%), than in higher concentrations. The combinations showed significant damage when compared to the negative controls, but it is not significant when compared to the corresponding individual concentrations of TCS and DEHP. The results observed by cytotoxicity and genotoxicity tests suggest possible changes in the cell redox state and consequent induction of DNA damage.
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    Avaliação do impacto da co-exposição do Triclosan e do Ftalato dehp sobre a viabilidade celular e a estabilidade genética, in vitro
    (Universidade Federal de São Paulo (UNIFESP), 2020-01-15) Duarte, Nathalia De Assis Aguilar [UNIFESP]; Barcelos, Gustavo Rafael Mazzaron [UNIFESP]; Universidade Federal de São Paulo
    Triclosan (TCS) is an antimicrobial agent widely used in Personal Care Products (PCPs) and Di-(2-ethylhydroxyl-phtalate) (DEHP) is a phthalate, a group of chemical compounds derived from phthalic acid, used in medical devices and plastic products with Polyvinyl Chloride (PVCs). As a result of extensive use, TCS and DEHP has been found in the environment and previous studies have demonstrated the interaction between their exposure and genotoxic damage to aquatic organisms. However, there is a shortage in the literature of these effects on human cells. Therefore, the aim of this study is to evaluate the cytotoxicity, genotoxicity, mutagenicity and interaction between TCS and DEPH compounds in HepG2 human hepatocarcinoma cell culture. Three different concentrations of each drug were chosen using the MTT test (0,10 μM, 1 μM e 10 μM) and 8 different combinations were evaluated later (e.g. TCS 10 μM + DEHP 1μM). The number of micronuclei (MN), nucleoplasmic bridges (NPBs), nuclear buds (NBUDs), nuclear division index (NDI), nuclear division cytotoxic index (NDCI), apoptotic and necrotic cells were evaluated. The results have shown that the three concentrations of TCS and the two highest DEHP concentrations increased the number of MN (p<0,05) as well as their combinations. The lower concentrations of both drugs had lower NDI and NDCI (p<0,05) when compared to the control group (DMSO 1%). The compounds showed synergistic and antagonist effects in several parameters analyzed. Finally, the results have shown a significant mutagenic (increase of MN) and cytostatic (decrease of NDI) and cytotoxic (decrease of NDCI) damage especially with co-exposure treatments, which is a more realistic model than studying drugs separately.