Toxicology Centre
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Item Molecular docking and in silico analysis of the pharmacokinetics, toxicological profile and differential gene expression of bioactive compounds from Cyrtopodium glutiniferum(Toxicology Reports, 2024-11) Araujo, Natalia Gonçalves Ribeiro; Carlos da Silva Junior, Francisco ; Santos, Lizandra; Batistuzzo de Medeiros, Silvia; Felzenszwalb, Israel; Araujo Lima, Carlos FernandoThe genus Cyrtopodium, from the Orchidaceae family, is widely used for its therapeutic properties in the treatment of tuberculosis, abscesses, urinary infection, and colds. C. glutiniferum, one of the species of this genus, is endemic in Brazil and largely used in herbal medicine. Thus, it is of great interest to recognize its composition, the properties of the molecules found in it. This study aimed to perform the in silico analysis of the main compounds from C. glutiniferum, on the platforms pKCSM, SwissADME, LAZAR, CLC-pred, ToxTree, DIGEPred, STRING, and Cytoscape. Further than this, the molecular docking was performed. The compounds present in the aqueous extract of C. glutiniferum were identified by UHPLC-MS/MS, finding Arbutin, Caffeic acid 4-O-glucoside, and Dihydroformononetin as the three most abundant molecules. The evaluation of the gastrointestinal absorption of Dihydroformononetin is given as high, also managing to cross the blood-brain barrier, while Arbutin can only be absorbed by the gastrointestinal tract and Caffeic acid 4-O-glucoside had very low absorption. Further analysis showed that Arbutin and Dihydroformononetin are possible leading molecules for drug synthesis, according to the prediction. Toxicological aspects were analysed, and no adverse effects were noted, but there were divergences in the mutagenic prediction of Arbutin and Dihydroformononetin, having different results in the used platforms, demonstrating that a cautious analysis and data insertion is needed in these tools to optimize them. The analysis of the differentially expressed genes predicted that the compounds can regulate several genes, including some genes associated with carcinogenesis and inflammation. The Molecular docking analysis showed high binding affinities of the molecules with different proteins. Therefore, C. glutiniferum demonstrates the potential to be used as a phytotherapeutic. The same was given through the in silico analysis of the three compounds found in the orchid, that show good individual potential.Item Unveiling the molecular effects of replacement and legacy PFASs: Transcriptomic analysis of zebrafish embryos reveals surprising similarities and potencies.(American Chemical Society, 2024-10-11) Mahoney, Hannah; Ankley, Phillip; Roberts, Catherine; Lamb, Alicia; Schultz, Matthew; Zhou, Yutong; Giesy, John; Brinkmann, MarkusThe prevalence of per- and poly fluoroalkyl substances (PFASs) in the environment has prompted restrictions on legacy PFASs due to their recognized toxic effects. Consequently, alternative “replacement” PFASs have been introduced and are prevalent in environmental matrices. Few studies have investigated the molecular effects of both legacy and replacement PFASs under short-term exposures. This study aimed to address this by utilizing transcriptomic sequencing to compare the molecular impacts of exposure to concentrations 0.001–5 mg/L of the legacy PFOS and two of its replacements, PFECHS and FBSA. Using zebrafish embryos, the research assessed apical effects (mortality, morphology, and growth), identified differentially expressed genes (DEGs) and enriched pathways, and determined transcriptomic points of departure (tPoDs) for each compound. Results indicated that PFOS exhibited the highest relative potency, followed by PFECHS and then FBSA. While similarities were observed among the ranked DEGs across all compounds, over-representation analysis revealed slight differences. Notably, PFOS demonstrated the lowest tPoD identified to date. These findings raise concerns regarding the safety of emerging replacement PFASs and challenge assumptions about PFAS toxicity solely resulting from their accumulative potential. As replacement PFASs proliferate in the environment, this study underscores the need for heightened scrutiny of their effects and questions current regulatory thresholds.Item Continental-scale nutrient and contaminant delivery by Pacific salmon(Nature, 2024-10-09) Brandt, Jessica E.; Wesner, Jeff F.; Ruggerone, Gregory; Jardine, Timothy D; Eagles-Smith, Collin A.; Ruso, Gabrielle E.; Stricker, Craig A.; Voss, Kristofor A.; Walters, David M.The movement of large amounts of nutrients by migrating animals has ecological benefits for recipient food webs that may be offset by co-transported contaminants. Salmon spawning migrations are archetypal of this process, carrying marine-derived materials to inland ecosystems where they stimulate local productivity but also enhance contaminant exposure. Pacific salmon abundance and biomass are higher now than in the last century, reflecting substantial shifts in community structure8 that probably altered nutrient versus contaminant delivery. Here we combined nutrient and contaminant concentrations with 40 years of annual Pacific salmon returns to quantify how changes in community structure influenced marine to freshwater inputs to western North America. Salmon transported tonnes of nutrients and kilograms of contaminants to freshwaters annually. Higher salmon returns (1976–2015) increased salmon-derived nutrient and contaminant inputs by 30% and 20%, respectively. These increases were dominated by pink salmon, which are short-lived, feed lower in marine food webs than other salmon species, and had the highest nutrient-to-contaminant ratios. As a result, the delivery of nutrients increased at a greater rate than the delivery of contaminants, and salmon inputs became more ecologically beneficial over time. Even still, contaminant loadings may represent exposure concerns for some salmon predators. The Pacific salmon example demonstrates how long-term environmental changes interact with nutrient and contaminant movement across large spatial scales and provides a model for exploring similar patterns with other migratory species.Item Assessment of Rapid and Conventional RT-qPCR-Based Systems for Wastewater Surveillance(ACS Publications, 2024-09-05) Asadi, Mohsen; Hamilton, Daniel; Shomachuk, Corwyn; Oloye, Femi F.; De Lange, Chantel; Liang, Jiaqi; Xia, Pu; Osunla, Charles A.; Cantin, Jenna; Mejia, Edgard M.; Gregorchuk, Branden S. J.; Becker, Michael G.; Mangat, Chand; Brinkmann, Markus; Jones, Paul D.; Giesy, John P.; McPhedran, Kerry M.Conventional wastewater surveillance (WS) relies on highly trained personnel, advanced instrumentation, and significant resources, making the development and use of simple, rapid, and sensitive alternative technologies valuable for reducing costs, time, and labor intensity. For the first time, this study investigated the use of two well-developed rapid systems, including the GeneXpert and LuminUltra, in parallel with a conventional WS reference methodology for the assessment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in three cities: Saskatoon, Prince Albert, and North Battleford, Saskatchewan, Canada. RNA extractions from wastewater samples were carried out for the conventional reference and LuminUltra methods, while GeneXpert was used for both raw and concentrated wastewater samples. Bland–Altman plots showed a combination of systematic bias and random error between these real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR)-based systems. Additionally, results indicated the reasonable performance of GeneXpert in viral detection with a sensitivity rate of >98%, as compared to the conventional reference methodology of 100% and LuminUltra with >65%. A Spearman correlation test showed meaningful relationships between the GeneXpert and conventional reference methodology viral level results across all cities, indicating GeneXpert’s reliability for accurate viral detection and disease prevalence determination, specifically in limited-resource communities, with a shorter processing time and cost-effectiveness in analysis.