Browsing by Issue Date, starting with "2019-11-29"
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- Infection with carcinogenic helminth parasites and its production of metabolites induces the formation of DNA-adductsPublication . Gouveia, Maria João; Brindley, Paul J.; Rinaldi, Gabriel; Gärtner, Fátima; da Costa, José M.C.; Vale, NunoBackground: Infections classified as group 1 biological carcinogens include the helminthiases caused by Schistosoma haematobium and Opisthorchis viverrini. The molecular mediators underlying the infection with these parasites and cancer remain unclear. Although carcinogenesis is a multistep process, we have postulated that these parasites release metabolites including oxysterols and estrogen-like metabolites that interact with host cell DNA. How and why the parasite produce/excrete these metabolites remain unclear. A gene encoding a CYP enzyme was identified in schistosomes and opisthorchiids. Therefore, it is reasonable hypothesized that CYP 450 might play a role in generation of pro-inflammatory and potentially carcinogenic compounds produced by helminth parasites such as oxysterols and catechol estrogens. Here, we performed enzymatic assays using several isoforms of CYP 450 as CYP1A1, 2E1 and 3A4 which are involved in the metabolism of chemical carcinogens that have been associated with several cancer. The main aim was the analysis of the role of these enzymes in production of helminth-associated metabolites and DNA-adducts. Method: The effect of cytochrome P450 enzymes CYP 1A1, 2E1 and 3A4 during the interaction between DNA, glycocholic acid and taurochenodeoxycholate sodium on the formation of DNA-adducts and metabolites associated with urogenital schistosomiasis (UGS) and opisthorchiasis was investigated in vitro. Liquid chromatography/mass spectrometry was used to detect and identify metabolites. Main findings: Through the enzymatic assays we provide a deeper understanding of how metabolites derived from helminths are formed and the influence of CYP 450. The assays using compounds similar to those previously observed in helminths as glycocholic acid and taurochenodeoxycholate sodium, allowed the detection of metabolites in their oxidized form and their with DNA. Remarkably, these metabolites were previously associated with schistosomiaisis and opisthorchiasis. Thus, in the future, it may be possible to synthesize this type of metabolites through this methodology and use them in cell lines to clarify the carcinogenesis process associated with these diseases. Principal conclusions: Metabolites similar to those detected in helminths are able to interact with DNA in vitro leading to the formation of DNA adducts. These evidences supported the previous postulate that imply helminth-like metabolites as initiators of helminthiases-associated carcinogenesis. Nonetheless, studies including these kinds of metabolites and cell lines in order to evaluate its potential carcinogenic are required.
- Ginkgo biloba L. Leaf Extract Protects HepG2 Cells Against Paraquat-Induced Oxidative DNA DamagePublication . Silva, Amélia; Silva, Sandra; Soares, Jorge; Martins-Gomes, Carlos; Teixeira, João Paulo; Leal, Fernanda; Gaivão, IsabelGinkgo biloba L. leaf extracts and herbal infusions are used worldwide due to the health benefits that are attributed to its use, including anti-neoplastic, anti-aging, neuro-protection, antioxidant and others. The aim of this study was to evaluate the effect of an aqueous Ginkgo biloba extract on HepG2 cell viability, genotoxicity and DNA protection against paraquat-induced oxidative damage. Exposure to paraquat (PQ), over 24 h incubation at 1.0 and 1.5 µM, did not significantly reduce cell viability but induced concentration and time-dependent oxidative DNA damage. Ginkgo biloba leaf extract produced dose-dependent cytotoxicity (IC50 = 540.8 ± 40.5 µg/mL at 24 h exposure), and short incubations (1 h) produced basal and oxidative DNA damage (>750 and 1500 µg/mL, respectively). However, lower concentrations (e.g., 75 µg/mL) of Ginkgo biloba leaf extract were not cytotoxic and reduced basal DNA damage, indicating a protective effect at incubations up to 4 h. On the other hand, longer incubations (24 h) induced oxidative DNA damage. Co-incubation of HepG2 cells for 4 h, with G. biloba leaf extract (75 µg/mL) and PQ (1.0 or 1.5 µM) significantly reduced PQ-induced oxidative DNA damage. In conclusion, the consumption of Ginkgo biloba leaf extract for long periods at high doses/concentrations is potentially toxic; however, low doses protect the cells against basal oxidative damage and against environmentally derived toxicants that induce oxidative DNA damage.
- Avaliação de Políticas Públicas – Plano Nacional de SaúdePublication . Caldas de Almeida, TeresaEnquadramento - Avaliação de políticas públicas: A avaliação de políticas consiste na implementação de princípios e métodos de avaliação para analisar e avaliar o conteúdo, a implementação e/ou o impacto de uma política; A avaliação deverá proporcionar informação baseada em evidências que seja credível, fiável e útil, permitindo a incorporação atempada de resultados, recomendações e lições para os processos de tomada de decisão.
- Aspergillosis in albatrossesPublication . Melo, Aryse Martins; Silva Filho, Rodolfo Pinho da; Poester, Vanice Rodrigues; Fernandes, Cristina Gevehr; von Groll, Andrea; Stevens, David A; Sabino, Raquel; Xavier, Melissa OrzechowskiAspergillosis is a respiratory fungal disease of importance in captive marine birds. The aim of this study was to describe the occurrence of aspergillosis in Thalassarche melanophris during rehabilitation events and to identify the etiological agent. All the albatrosses that were received for rehabilitation and died within a 2-year period were included in the study. The proportionate mortality rate caused by aspergillosis was 21.4% (3/14). One of the etiological agents was Aspergillus flavus/oryzae lineage, and the other was A. fumigatus sensu stricto. Our study suggests that aspergillosis can act as a limiting factor in the rehabilitation of albatrosses.