Ferroptosis is evolving as a highly promising approach to combat difficult-to-treat tumour entities including therapy-refractory and dedifferentiating cancers. Recently, ferroptosis suppressor protein-1 (FSP1), along with extramitochondrial ubiquinone or exogenous vitamin K and NAD(P)H/H as an electron donor, has been identified as the second ferroptosis-suppressing system, which efficiently prevents lipid peroxidation independently of the cyst(e)ine-glutathione (GSH)-glutathione peroxidase 4 (GPX4) axis. To develop FSP1 inhibitors as next-generation therapeutic ferroptosis inducers, here we performed a small molecule library screen and identified the compound class of 3-phenylquinazolinones (represented by icFSP1) as potent FSP1 inhibitors.
View Article and Find Full Text PDFArch Toxicol
January 2022
Polybrominated diphenyl ethers (PBDEs) are ubiquitous persistent organic pollutants (POPs) that are known neuroendocrine disrupting chemicals with adverse neurodevelopmental effects. PBDEs may act as risk factors for autism spectrum disorders (ASD), characterized by abnormal psychosocial functioning, although direct evidence is currently lacking. Using a translational exposure model, we tested the hypothesis that maternal transfer of a commercial mixture of PBDEs, DE-71, produces ASD-relevant behavioral and neurochemical deficits in female offspring.
View Article and Find Full Text PDFInt J Hyg Environ Health
June 2021
Background: Concentrations of persistent organic pollutants (POPs) have been associated with an increased type 2 diabetes (T2D) risk. It remains unclear whether POPs are also associated with the risk of diabetes complications including neuropathy and evidence on this topic is scarce. We aimed to investigate the hypothesis that low-dose background concentrations of POPs were positively associated with distal sensorimotor polyneuropathy (DSPN).
View Article and Find Full Text PDFAccidental spills or illegal discharges of pesticides in aquatic ecosystems can lead to exposure levels that strongly exceed authorized pesticide concentrations, causing major impacts on aquatic ecosystems. Such short-term events often remain undetected in regular monitoring programs with infrequent sampling. In early spring 2015, we identified a catastrophic pesticide spill with the insecticide cypermethrin in the Holtemme River, Germany.
View Article and Find Full Text PDFSampling points belonging to the Harz National Park river system, Germany, were selected between the period of 2014 and 2017 for monitoring polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in water, air, and sediment. Triolein-containing Virtual Organisms (VO) were employed to assess the levels of chemicals in water, air and triolein as surrogate for natural fat. To avoid overestimation of the concentrations 20 performance reference compounds (PRCs)-16 PRCs-PAHs and 4 PRCs-PCBs were covering the range of properties of native compounds.
View Article and Find Full Text PDFIntroduction: Reliability in the use of placentome (including placenta, umbilical cord, and cord blood) biomarkers requires an understanding of their distributions. Here we aim to develop a simple and proper placenta sampling scheme, and to evaluate the placental distributions of biomarkers.
Methods: We developed a continuous cooling chain protocol off delivery room and cryo-subsampling method for placenta sampling.
Organochlorine pesticides (OCPs) were analyzed in three different ages (half-, 1.5-, 2.5-year-old) for needles and semi permeable membrane devices (SPMDs) at three deployment periods from sea level to 1881 meter above sea level.
View Article and Find Full Text PDFSci Total Environ
January 2020
Sci Total Environ
December 2019
Exposomics is assessment of organism exposure to high priority environmental pollutants in an ecosystem using OMIC technologies. A virtual organism (VO) is an artificial property-tool (OMIC) reflecting exposomic process in compartments of real organisms. The exposomics of aquatic organisms inhabiting Lake Victoria (L.
View Article and Find Full Text PDFRecent European regulations have indicated the need for new bioanalytical screening methods capable of monitoring dioxin and dioxin-like compounds in foodstuffs and environmental samples, cost-effectively and with a quicker turnaround. Cryo-cells of the hepatic H4IIE line preserved in 96-well plates were exposed to sample extracts prepared from various foodstuffs and analysed for their content of dioxins and dioxin-like compounds by means of the 7-Ethoxyresorufin-O-Deethylase (EROD)-assay in two laboratories. Assay data were compared between both laboratories and results from instrumental analysis used as a confirmatory method.
View Article and Find Full Text PDFPerformance reference compounds (PRCs) are neutral organic compounds, introduced in a passive sampler prior deployment for the assessment of in situ sampling rate. In this study, evaluation of in situ sampling rates of 16 C-PAH-PRCs with moderate and high hydrophobicity was established to provide an overall correction factor for variations in virtual organism (VO) uptake rates of the analytes of interest. In situ sampling rate was compared to an empirical model during sampling campaign in 2011 with VO in 12 different sites along the Three Gorges Reservoir (TGR) in China.
View Article and Find Full Text PDFBromocarbazoles and chlorocarbazoles are emerging environmental contaminants that have been reported to be persistent and possessing dioxin-like toxicity; however, their photodegradative fate in water is unknown. The photodegradation of 3-bromocarbazole, 3-chlorocarbazole, and 3,6-dichlorocarbazole was determined in ultrapure water. They proceeded by direct photolysis and followed first-order kinetics.
View Article and Find Full Text PDFPolychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) were detected in 86 humic topsoil layers and in a subset of 11 randomly selected top mineral forest soils at the depths of 0-5cm and 5-10cm collected from different federal states of Germany. The distribution of these persistent organic pollutants (POPs) in humic topsoils with respect to vegetation cover (coniferous vs. deciduous vs.
View Article and Find Full Text PDFThis study involves the monitoring of organic pollutants using transplanted mussels (Mytilus galloprovincialis) as bioindicator organisms and semipermeable membrane devices (SPMDs) as passive samplers. Mussels and SPMDs were deployed to marinas, shipyards and shipbreaking yards on the coastal area of Turkey and retrieved after 60 days. Polycyclic aromatic hydrocarbons (PAH), polychlorinated biphenyls (PCB) and organochlorine pesticide (OCP) compounds were analysed with high-resolution GC-MS.
View Article and Find Full Text PDFEnviron Sci Pollut Res Int
March 2017
Polycyclic aromatic hydrocarbons (PAHs) were analyzed at different altitudes of Taurus Mountains in semipermeable membrane devices (SPMD) and in half-, one-and-a-half-, and two-and-a-half-year-old pine needles. SPMDs were deployed for three different exposure periods: March to September (Summer), September to March (Winter), and March to March (whole year) at eight sites where needle samples were collected. The values of PAHs in needles were between 4.
View Article and Find Full Text PDFIn the German Calcareous Alps at the Zugspitze, percolated water close to a permafrost bedrock in a tunnel system was monitored long-term for polychlorinated dibenzo-p-dioxins (PCDD), polychlorinated dibenzofurans (PCDF), polychlorinated biphenyls (PCB), polycyclic aromatic hydrocarbons (PAH), and 28 organochlorine pesticides (OCP). Semi-permeable membrane devices (SPMD) were deployed in a temporary surface water system at the Zugspitze plateau and analysed for PCB, PAH, and OCP. The high-volume water sampling was successfully implemented and all compounds were identified in the water percolated through the Karst system.
View Article and Find Full Text PDFDioxins and dioxin-like compounds can be analyzed by bioanalytical screening methods to evaluate their biotoxicity. In vitro bioassays, based on 7-ethoxyresorufin-O-deethylase (EROD) and the activity of cytochrome P450 1A1 and the aryl hydrogen receptor (AhR) pathway, are employed for the evaluation of bioanalytical equivalents (BEQ) of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) from a wide variety of sample matrices. Here, we present the evaluation of 11 humic soil samples derived from forest stands across Germany and a comparison of the BEQ values against toxic equivalents (TEQ, PCDD/Fs+PCBs) derived by chemical analysis.
View Article and Find Full Text PDFThe occurrence of bromocarbazoles and chlorocarbazoles was studied in 86 forest soil samples from different regions in Germany. Carbazole, 3-chlorocarbazole, 3-bromocarbazole and 3,6-dibromocarbazole were qualitatively detected in the humic layer of 59 soil samples with bromocarbazoles reported here for the first time in soil. Furthermore, the halogenated carbazoles, PCDD/Fs and PCBs were detected in the humic and mineral soil horizons (0-5 cm and 5-10 cm) of a subset of 11 soil samples subjected to quantitative analysis.
View Article and Find Full Text PDFPersistent and emerging organic pollutants were sampled in September 2012 and 2013 at a sampling site in front of the Three Gorges Dam near Maoping (China) in a water depth between 11 and 61 m to generate a depth profile of analytes. A novel compact water sampling system with self-packed glass cartridges was employed for the on-site enrichment of approximately 300 L of water per sample to enable the detection of low analytes levels in the picogram per liter-scale in the large water body. The overall performance of the sampling system was acceptable for the qualitative detection of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), perfluoroalkylic acids (PFAAs), pharmaceutical residues and polar pesticides.
View Article and Find Full Text PDFPolycyclic aromatic hydrocarbon (PAHs) and polychlorinated biphenyls (PCBs) accumulated by semipermeable membrane device (SPMD)-based virtual organisms (VOs) and local feral fish were studied in Three Gorges Reservoir (TGR), China. VOs were deployed at seven sites in TGR for two periods in 2009 and 5 species of fish with different living habitats and feeding habits collected in the same periods from two counties in TGR. The concentration and profile of PAHs and PCBs in fish were quite different from those in VOs.
View Article and Find Full Text PDFOrganochlorine pesticides (OCP) are widely distributed environmental pollutants. Due to their persistence and toxicity, it is important to know their fluxes and spatial and temporal distribution in the environment. In this study, a new procedure to estimate OCP concentration based on a set of performance reference compounds (PRCs) was used.
View Article and Find Full Text PDFEndosulfan - an agricultural insecticide and banned by Stockholm Convention - is produced as a 2:1 to 7:3 mixture of isomers endosulfan I (ESI) and endosulfan II (ESII). Endosulfan is transformed under aerobic conditions into endosulfan sulfate (ESS). The study shows for 76 sampling locations in German forests that endosulfan is abundant in all samples with an opposite ratio between the ESI and ESII than the technical product, where the main metabolite ESS is found with even higher abundance.
View Article and Find Full Text PDFEven early life in utero cannot provide a safe place for newborns. The first acquaintance with chemicals takes place in utero and/or with mother's milk after delivery. Besides legislations and bans to persistent organic pollutants (POPs), these chemicals are still affecting the general population especially the children as they are one of the populations most susceptible to chemicals, and also the health problems may arise in the future.
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