Search Results (7)

Recently, toxicological and epidemiological research has provided strong support for the unfavorable effects of bisphenol-A (BPA, 2,2′-bis(4-hydroxyphenyl) propane) on myogenesis and its underlying mechanisms. Researchers have therefore been looking for new strategies to prevent or mitigate these injurious effects of BPA on the human body. It has been found that plant extracts may act as potential therapeutic agents or functional foods, preventing human diseases caused by BPA. We previously reported that Ficus lindsayana (FL) extract exhibits anti-inflammation activity in macrophages via suppressing the expression of inflammation-related molecules and anti-insulin resistance in inflammation-treated adipocytes. In this study, we investigated whether Ficus lindsayana leaf extract (FLLE) protects C2C12 mouse myoblasts against the suppressive effects of BPA on myogenic differentiation. The viability of BPA-stimulated C2C12 myoblasts was significantly increased when co-treated with FLLE (200 µg/mL), suggesting that the extract may lessen the inhibitory effects of BPA on cell division. We also found that FLLE significantly increased neo-myotube formation by inducing the fusion of myoblasts into multinucleated myotubes when compared to the BPA-treated control cells, without impacting cell viability. In addition, the levels of myogenin and myocyte enhancer factor 2A (MEF2A), which are crucial markers and regulators of myogenesis, were markedly increased by the addition of FLLE (50 µg/mL) to the BPA-treated C2C12 cells. This finding suggests that FLLE effectively improved myogenic differentiation in BPA-exposed myoblasts. FLLE treatment (50 µg/mL) significantly raised total Akt protein levels in the BPA-treated C2C12 cells, enhancing protein phosphorylation. In addition, FLLE (50 µg/mL) obviously increased the phosphorylation levels of p70S6K and 4E-BP1, key downstream targets of the Akt/mTOR signaling cascade, by elevating total p70S6K and 4E-BP1 levels. These results suggest that FLLE diminishes the decline in myogenic differentiation induced by BPA via the regulation of the myocyte differentiation-related signaling pathway. The information obtained from this study demonstrates the health benefits of this plant, which warrants further investigation as an alternative medicine, functional ingredient, or food supplement that can prevent the negative health effects of BPA or other toxicants. Full article

The widely used plasticizer bisphenol-A (BPA) is well-known for producing neurodegeneration and cognitive disorders, following acute and long-term exposure. Although some of the BPA actions involved in these effects have been unraveled, they are still incompletely known. Basal forebrain cholinergic neurons (BFCN) regulate memory and learning processes and their selective loss, as observed in Alzheimer’s disease and other neurodegenerative diseases, leads to cognitive decline. In order to study the BPA neurotoxic effects on BFCN and the mechanisms through which they are induced, 60-day old Wistar rats were used, and a neuroblastoma cholinergic cell line from the basal forebrain (SN56) was used as a basal forebrain cholinergic neuron model. Acute treatment of rats with BPA (40 µg/kg) induced a more pronounced basal forebrain cholinergic neuronal loss. Exposure to BPA, following 1- or 14-days, produced postsynaptic-density-protein-95 (PSD95), synaptophysin, spinophilin, and N-methyl-D-aspartate-receptor-subunit-1 (NMDAR1) synaptic proteins downregulation, an increase in glutamate content through an increase in glutaminase activity, a downregulation in the vesicular-glutamate-transporter-2 (VGLUT2) and in the WNT/β-Catenin pathway, and cell death in SN56 cells. These toxic effects observed in SN56 cells were mediated by overexpression of histone-deacetylase-2 (HDAC2). These results may help to explain the synaptic plasticity, cognitive dysfunction, and neurodegeneration induced by the plasticizer BPA, which could contribute to their prevention. Full article

Humans are constantly exposed to many environmental pollutants, some of which have been largely acknowledged as key factors in the development of metabolic disorders such as diabetes and obesity. These chemicals have been classified as endocrine-disrupting chemicals (EDCs) and, more recently, since they can interfere with metabolic functions, they have been renamed as metabolism-disrupting chemicals (MDCs). MDCs are present in many consumer products, including food packaging, personal care products, plastic bottles and containers, and detergents. The scientific literature has ever-increasingly focused on insulin-releasing pancreatic β-cells as one of the main targets for MDCs. Evidence highlights that these substances may disrupt glucose homeostasis by altering pancreatic β-cell physiology. However, their potential impact on glucagon-secreting pancreatic α-cells remains poorly known despite the essential role that this cellular type plays in controlling glucose metabolism. In the present study, we have selected seven paradigmatic MDCs representing major toxic classes, including bisphenols, phthalates, perfluorinated compounds, metals, and pesticides. By using an in vitro cell-based model, the pancreatic α-cell line αTC1-9, we have explored the effects of these compounds on pancreatic α-cell viability, gene expression, and secretion. We found that cell viability was moderately affected after bisphenol-A (BPA), bisphenol-F (BPF), and perfluorooctanesulfonic acid (PFOS) exposure, although cytotoxicity was relatively low. In addition, all bisphenols, as well as di(2-ethylhexyl) phthalate (DEHP) and cadmium chloride (CdCl₂), promoted a marked decreased on glucagon secretion, together with changes in the expression of glucagon and/or transcription factors involved in cell function and identity, such as Foxo1 and Arx. Overall, our results indicated that most of the selected chemicals studied caused functional alterations in pancreatic α-cells. Moreover, we revealed, for the first time, their direct effects on key molecular aspects of pancreatic α-cell biology. Full article

Aquaculture, a mass supplier of seafood, relies on plastic materials that may contain the endocrine disruptors bisphenol-A (BPA) and tert-octylphenol (t-OCT). These pollutants present toxicity to Artemia, the live aquaculture feed, and are transferred through it to the larval stages of the cultured organisms. The purpose of this work is the development and validation of an analytical method to determine BPA and t-OCT in Artemia and their culture medium, using n-octylphenol as the internal standard. Extraction of the samples was performed with H₂O/TFA (0.08%)–methanol (3:1), followed by SPE. Analysis was performed in a Nucleosil column with mobile phases A (95:5, v/v, 0.1% TFA in H₂O:CH₃CN) and B (5:95, v/v, 0.08% TFA in H₂O:CH₃CN). Calibration curves were constructed in the range of concentrations expected following a 24 h administration of BPA (10 μg/mL) or t-OCT (0.5 μg/mL), below their respective LC₅₀. At the end of exposure to the pollutants, their total levels appeared reduced by about 32% for BPA and 35% for t-OCT, and this reduction could not be accounted for by photodegradation (9–19%). The developed method was validated in terms of linearity, accuracy, and precision, demonstrating the uptake of BPA and t-OCT in Artemia. Full article

Untargeted lipidomics has previously been applied to the study of daphnids and the discovery of biomarkers that are indicative of toxicity. Typically, liquid chromatography—mass spectrometry is used to measure the changes in lipid abundance in whole-body homogenates of daphnids, each only ca. 3 mm in length which limits any biochemical interpretation of site-specific toxicity. Here, we applied mass spectrometry imaging of Daphnia magna to combine untargeted lipidomics with spatial resolution to map the molecular perturbations to defined anatomical regions. A desorption electrospray ionization—mass spectrometry (DESI-MS) method was optimized and applied to tissue sections of daphnids exposed to bisphenol-A (BPA) compared to unexposed controls, generating an untargeted mass spectrum at each pixel (35 µm²/pixel) within each section. First, unique lipid profiles from distinct tissue types were identified in whole-body daphnids using principal component analysis, specifically distinguishing appendages, eggs, eye, and gut. Second, changes in the lipidome were mapped over four stages of normal egg development and then the effect of BPA exposure on the egg lipidome was characterized. The primary perturbations to the lipidome were annotated as triacylglycerides and phosphatidylcholine, and the distributions of the individual lipid species within these classes were visualized in whole-body D. magna sections as ion images. Using an optimized DESI-MS workflow, the first ion images of D. magna tissue sections were generated, mapping both their baseline and BPA-perturbed lipidomes. Full article

Bisphenol-A (BPA), bisphenol A glycerolate dimethacrylate (Bis-GMA), triethylene glycol dimethacrylate (TEGDMA), and urethane dimethacrylate (UDMA) are organic monomers that can be released from dental composites into the oral cavity. Over specific concentrations, they can act as endocrine disruptors or cause toxic effects. The purpose of this work is to develop and validate an analytical method to determine BPA, Bis-GMA, TEGDMA, and UDMA monomers released from synthetic dental resins in artificial saliva. The method was validated before its application to new hybrid ceramic materials used in computer-aided design and computer-aided manufacturing (CAD/CAM) restorations to determine the release of monomers in various time intervals (e.g., 24 h, and 7, 14, 30, and 60 days), both in methanolic solutions, as well as in artificial saliva. Chromatographic analysis was performed isocratically on a Perfect Sil Target ODS-3 analytical column (250 mm × 4.6 mm, 5 µm) with CH₃CN/H₂O, 58/42% v/v as mobile phase within 23 min. The developed method was validated in terms of selectivity, linearity, accuracy, and precision. Full article

Bisphenol-A (BPA) is a ubiquitous endocrine-disrupting chemical. Recently, many issues have arisen surrounding the disease pathogenesis of BPA. Therefore, several studies have been conducted to investigate the proteomic biomarkers of BPA that are associated with disease processes. However, studies on identifying highly sensitive biological cell model systems in determining BPA health risk are lacking. Here, we determined suitable cell model systems and potential biomarkers for predicting BPA-mediated disease using the bioinformatics tool Pathway Studio. We compiled known BPA-mediated diseases in humans, which were categorized into five major types. Subsequently, we investigated the differentially expressed proteins following BPA exposure in several cell types, and analyzed the efficacy of altered proteins to investigate their associations with BPA-mediated diseases. Our results demonstrated that colon cancer cells (SW480), mammary gland, and Sertoli cells were highly sensitive biological model systems, because of the efficacy of predicting the majority of BPA-mediated diseases. We selected glucose-6-phosphate dehydrogenase (G6PD), cytochrome b-c1 complex subunit 1 (UQCRC1), and voltage-dependent anion-selective channel protein 2 (VDAC2) as highly sensitive biomarkers to predict BPA-mediated diseases. Furthermore, we summarized proteomic studies in spermatozoa following BPA exposure, which have recently been considered as another suitable cell type for predicting BPA-mediated diseases. Full article