Subjects -> ENVIRONMENTAL STUDIES (Total: 925 journals)
    - ENVIRONMENTAL STUDIES (822 journals)
    - POLLUTION (31 journals)
    - TOXICOLOGY AND ENVIRONMENTAL SAFETY (54 journals)
    - WASTE MANAGEMENT (18 journals)

ENVIRONMENTAL STUDIES (822 journals)                  1 2 3 4 5 | Last

Showing 1 - 200 of 378 Journals sorted alphabetically
ACS Chemical Health & Safety     Hybrid Journal   (Followers: 4)
ACS ES&T Engineering     Hybrid Journal   (Followers: 2)
Acta Brasiliensis     Open Access  
Acta Ecologica Sinica     Open Access   (Followers: 9)
Acta Environmentalica Universitatis Comenianae     Open Access  
Acta Limnologica Brasiliensia     Open Access   (Followers: 3)
Acta Oecologica     Hybrid Journal   (Followers: 11)
Acta Regionalia et Environmentalica     Open Access   (Followers: 1)
Advanced Electronic Materials     Hybrid Journal   (Followers: 5)
Advanced Energy and Sustainability Research     Open Access   (Followers: 4)
Advanced Sustainable Systems     Hybrid Journal   (Followers: 5)
Advances in Ecological Research     Full-text available via subscription   (Followers: 41)
Advances in Environmental Chemistry     Open Access   (Followers: 9)
Advances in Environmental Sciences - International Journal of the Bioflux Society     Open Access   (Followers: 12)
Advances in Environmental Technology     Open Access  
Advances in Life Science and Technology     Open Access   (Followers: 10)
Advances in Tropical Biodiversity and Environmental Sciences     Open Access   (Followers: 3)
Aeolian Research     Hybrid Journal   (Followers: 6)
African Journal of Environmental Science and Technology     Open Access   (Followers: 2)
Agricultura Tecnica     Open Access   (Followers: 1)
Agricultural & Environmental Letters     Open Access   (Followers: 3)
Agro-Science     Full-text available via subscription   (Followers: 1)
Agroecological journal     Open Access  
Agronomy for Sustainable Development     Open Access   (Followers: 18)
Agrosystems, Geosciences & Environment     Open Access   (Followers: 3)
Amazon's Research and Environmental Law     Open Access   (Followers: 2)
Ambiência     Open Access  
Ambiens. Revista Iberoamericana Universitaria en Ambiente, Sociedad y Sustentabilidad     Open Access  
American Journal of Energy and Environment     Open Access   (Followers: 4)
American Journal of Environmental Engineering     Open Access   (Followers: 6)
American Journal of Environmental Protection     Open Access   (Followers: 3)
American Journal of Environmental Sciences     Open Access   (Followers: 8)
American Naturalist     Full-text available via subscription   (Followers: 78)
Annals of Civil and Environmental Engineering     Open Access   (Followers: 1)
Annals of Environmental Science and Toxicology     Open Access   (Followers: 2)
Annals of GIS     Open Access   (Followers: 29)
Annual Review of Ecology, Evolution, and Systematics     Full-text available via subscription   (Followers: 80)
Annual Review of Environment and Resources     Full-text available via subscription   (Followers: 16)
Annual Review of Pharmacology and Toxicology     Full-text available via subscription   (Followers: 36)
Annual Review of Resource Economics     Full-text available via subscription   (Followers: 9)
Applied and Environmental Soil Science     Open Access   (Followers: 14)
Applied Ecology and Environmental Sciences     Open Access   (Followers: 28)
Applied Environmental Education & Communication     Hybrid Journal   (Followers: 15)
Applied Journal of Environmental Engineering Science     Open Access   (Followers: 1)
Aquatic Ecology     Hybrid Journal   (Followers: 38)
Aquatic Toxicology     Hybrid Journal   (Followers: 23)
Arcada : Revista de conservación del patrimonio cultural     Open Access  
Architecture, Civil Engineering, Environment     Open Access   (Followers: 3)
Archives des Maladies Professionnelles et de l'Environnement     Full-text available via subscription  
Archives of Environmental and Occupational Health     Hybrid Journal   (Followers: 10)
Archives of Environmental Contamination and Toxicology     Hybrid Journal   (Followers: 12)
Archives of Environmental Protection     Open Access   (Followers: 3)
Archives of Toxicology     Hybrid Journal   (Followers: 20)
Arctic Environmental Research     Open Access  
Asian Journal of Environment & Ecology     Open Access  
Asian Journal of Rural Development     Open Access   (Followers: 9)
Asian Review of Environmental and Earth Sciences     Open Access   (Followers: 1)
ATBU Journal of Environmental Technology     Open Access   (Followers: 1)
Atmospheric and Climate Sciences     Open Access   (Followers: 32)
Atmospheric Environment     Hybrid Journal   (Followers: 72)
Atmospheric Environment : X     Open Access   (Followers: 2)
Augm Domus : Revista electrónica del Comité de Medio Ambiente de AUGM     Open Access  
Austral Ecology     Hybrid Journal   (Followers: 16)
Australasian Journal of Environmental Management     Hybrid Journal   (Followers: 8)
Australasian Journal of Human Security     Full-text available via subscription   (Followers: 1)
Australian Journal of Environmental Education     Full-text available via subscription   (Followers: 9)
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 13)
Basic and Applied Ecology     Hybrid Journal   (Followers: 21)
Behavioral Ecology     Hybrid Journal   (Followers: 56)
Behavioral Ecology and Sociobiology     Hybrid Journal   (Followers: 35)
Biocenosis     Open Access  
Biochar     Hybrid Journal   (Followers: 1)
Biodegradation     Hybrid Journal   (Followers: 2)
Biodiversity     Hybrid Journal   (Followers: 23)
Biofouling: The Journal of Bioadhesion and Biofilm Research     Hybrid Journal   (Followers: 2)
Bioremediation Journal     Hybrid Journal   (Followers: 4)
BioRisk     Open Access   (Followers: 2)
BMC Ecology     Open Access   (Followers: 24)
Boletín Instituto de Derecho Ambiental y de los Recursos Naturales     Open Access  
Boletín Semillas Ambientales     Open Access  
Boston College Environmental Affairs Law Review     Open Access   (Followers: 5)
Bothalia : African Biodiversity & Conservation     Open Access  
Built Environment     Full-text available via subscription   (Followers: 5)
Bulletin of Environmental Contamination and Toxicology     Hybrid Journal   (Followers: 10)
Bulletin of the American Meteorological Society     Open Access   (Followers: 60)
Bumi Lestari Journal of Environment     Open Access  
Canadian Journal of Earth Sciences     Hybrid Journal   (Followers: 21)
Canadian Journal of Remote Sensing     Full-text available via subscription   (Followers: 51)
Canadian Journal of Soil Science     Full-text available via subscription   (Followers: 12)
Canadian Water Resources Journal     Hybrid Journal   (Followers: 18)
Capitalism Nature Socialism     Hybrid Journal   (Followers: 20)
Carbon Capture Science & Technology     Open Access   (Followers: 5)
Carbon Resources Conversion     Open Access   (Followers: 2)
Case Studies in Chemical and Environmental Engineering     Open Access  
Cell Biology and Toxicology     Hybrid Journal   (Followers: 10)
Chain Reaction     Full-text available via subscription  
Challenges in Sustainability     Open Access   (Followers: 9)
Chemical Research in Toxicology     Hybrid Journal   (Followers: 22)
Chemico-Biological Interactions     Hybrid Journal   (Followers: 3)
Chemosphere     Hybrid Journal   (Followers: 16)
Child and Adolescent Mental Health     Hybrid Journal   (Followers: 68)
Ciencia, Ambiente y Clima     Open Access  
City and Environment Interactions     Open Access   (Followers: 2)
Civil and Environmental Engineering     Open Access   (Followers: 6)
Civil and Environmental Engineering Reports     Open Access   (Followers: 3)
Civil and Environmental Research     Open Access   (Followers: 15)
CLEAN - Soil, Air, Water     Hybrid Journal   (Followers: 17)
Clean Technologies and Environmental Policy     Hybrid Journal   (Followers: 4)
Cleaner Environmental Systems     Open Access   (Followers: 4)
Cleaner Production Letters     Hybrid Journal   (Followers: 5)
Cleanroom Technology     Full-text available via subscription   (Followers: 1)
Climate and Energy     Full-text available via subscription   (Followers: 5)
Climate Change Ecology     Open Access   (Followers: 10)
Climate Change Economics     Hybrid Journal   (Followers: 35)
Climate Policy     Hybrid Journal   (Followers: 45)
Climate Resilience and Sustainability     Open Access   (Followers: 18)
Coastal Engineering Journal     Hybrid Journal   (Followers: 7)
Cogent Environmental Science     Open Access  
Columbia Journal of Environmental Law     Open Access   (Followers: 12)
Computational Ecology and Software     Open Access   (Followers: 9)
Computational Water, Energy, and Environmental Engineering     Open Access   (Followers: 5)
Conservation and Society     Open Access   (Followers: 12)
Conservation Letters     Open Access   (Followers: 48)
Conservation Science     Open Access   (Followers: 26)
Consilience : The Journal of Sustainable Development     Open Access   (Followers: 2)
Contemporary Problems of Ecology     Hybrid Journal   (Followers: 4)
Critical Reviews in Environmental Science and Technology     Hybrid Journal   (Followers: 11)
Critical Reviews in Toxicology     Hybrid Journal   (Followers: 26)
Cuadernos de Investigación Geográfica / Geographical Research Letters     Open Access  
Culture, Agriculture, Food and Environment     Hybrid Journal   (Followers: 21)
Culture, Agriculture, Food and Environment     Hybrid Journal   (Followers: 9)
Current Environmental Health Reports     Hybrid Journal   (Followers: 1)
Current Forestry Reports     Hybrid Journal   (Followers: 1)
Current Landscape Ecology Reports     Hybrid Journal   (Followers: 2)
Current Opinion in Environmental Science & Health     Hybrid Journal  
Current Opinion in Environmental Sustainability     Hybrid Journal   (Followers: 14)
Current Research in Ecological and Social Psychology     Open Access   (Followers: 5)
Current Research in Environmental Sustainability     Open Access   (Followers: 2)
Current Research in Green and Sustainable Chemistry     Open Access  
Current Research in Microbiology     Open Access   (Followers: 21)
Current Sustainable/Renewable Energy Reports     Hybrid Journal   (Followers: 7)
Die Bodenkultur : Journal of Land Management, Food and Environment     Open Access  
Disaster Prevention and Management     Hybrid Journal   (Followers: 29)
Discover Sustainability     Open Access   (Followers: 2)
disP - The Planning Review     Hybrid Journal   (Followers: 1)
Drug and Chemical Toxicology     Hybrid Journal   (Followers: 13)
Duke Environmental Law & Policy Forum     Open Access   (Followers: 7)
Dynamiques Environnementales     Open Access  
E3S Web of Conferences     Open Access  
Earth and Environmental Science Transactions of the Royal Society of Edinburgh     Hybrid Journal   (Followers: 5)
Earth Interactions     Open Access   (Followers: 11)
Earth Science Informatics     Hybrid Journal   (Followers: 5)
Earth System Governance     Open Access  
Earth System Science Data (ESSD)     Open Access   (Followers: 7)
Earth Systems and Environment     Hybrid Journal   (Followers: 2)
EchoGéo     Open Access  
Eco-Thinking     Open Access   (Followers: 2)
Ecocycles     Open Access   (Followers: 4)
Ecohydrology     Hybrid Journal   (Followers: 8)
Ecohydrology & Hydrobiology     Full-text available via subscription   (Followers: 4)
Ecologia Aplicada     Open Access  
Ecología en Bolivia     Open Access  
Ecological Applications     Full-text available via subscription   (Followers: 135)
Ecological Chemistry and Engineering S     Open Access   (Followers: 2)
Ecological Complexity     Hybrid Journal   (Followers: 7)
Ecological Engineering     Hybrid Journal   (Followers: 4)
Ecological Indicators     Hybrid Journal   (Followers: 20)
Ecological Informatics     Hybrid Journal   (Followers: 3)
Ecological Management & Restoration     Hybrid Journal   (Followers: 15)
Ecological Modelling     Hybrid Journal   (Followers: 69)
Ecological Monographs     Full-text available via subscription   (Followers: 36)
Ecological Processes     Open Access   (Followers: 2)
Ecological Questions     Open Access   (Followers: 4)
Ecological Research     Hybrid Journal   (Followers: 10)
Ecological Restoration     Full-text available via subscription   (Followers: 21)
Ecologist, The     Full-text available via subscription   (Followers: 22)
Ecology     Full-text available via subscription   (Followers: 340)
Ecology and Evolution     Open Access   (Followers: 90)
Ecology Letters     Hybrid Journal   (Followers: 238)
EcoMat : Functional Materials for Green Energy and Environment     Open Access  
Economics and Policy of Energy and the Environment     Full-text available via subscription   (Followers: 13)
Économie rurale     Open Access   (Followers: 3)
Ecoprint : An International Journal of Ecology     Open Access   (Followers: 4)
Ecopsychology     Hybrid Journal   (Followers: 7)
Ecosphere     Open Access   (Followers: 8)
Ecosystem Services     Hybrid Journal   (Followers: 7)
Ecosystems     Hybrid Journal   (Followers: 31)
Ecosystems and People     Open Access   (Followers: 2)
Ecotoxicology     Hybrid Journal   (Followers: 9)
Ecotoxicology and Environmental Safety     Hybrid Journal   (Followers: 10)
Ecotrophic : Journal of Environmental Science     Open Access  
Ecozon@ : European Journal of Literature, Culture and Environment     Open Access   (Followers: 4)
Éducation relative à l'environnement     Open Access  
Electronic Green Journal     Open Access   (Followers: 4)
Empowering Sustainability International Journal     Open Access   (Followers: 5)
Energy & Environmental Science     Hybrid Journal   (Followers: 32)
Energy and Climate Change     Hybrid Journal   (Followers: 8)
Energy and Environment Focus     Free   (Followers: 7)
Energy and Environment Research     Open Access   (Followers: 13)
Energy and Environmental Engineering     Open Access   (Followers: 5)

        1 2 3 4 5 | Last

Similar Journals
Journal Cover
Archives of Toxicology
Journal Prestige (SJR): 1.541
Citation Impact (citeScore): 5
Number of Followers: 20  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1432-0738 - ISSN (Online) 0340-5761
Published by Springer-Verlag Homepage  [2469 journals]
  • Toxicokinetics, in vivo metabolic profiling, and in vitro metabolism of
           gelsenicine in rats

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      Abstract: Abstract Gelsenicine, mainly isolated from Gelsemium elegans Benth., is one of the most toxic alkaloids. The lack of information on gelsenicine leads to inaccurate risk and poisoning evaluation. In this study, the metabolic profiling and toxicokinetics of gelsenicine was studied by ultra-high performance liquid chromatography (UPLC) with quadrupole time-of-flight (Q-ToF) and tandem mass spectrometry in rats after intraperitoneal (i.p., 40 μg/kg) and intragastric (i.g., 60 μg/kg) administration. After i.p. administration, the area under the curve (AUC), the apparent volume of distribution (V), and the total body clearance (CL/F) of gelsenicine in plasma were 3.79 μg/L h, 38.47 L/kg, and 11.87 mL/h kg, respectively. After i.g. administration, the corresponding values were slightly increased (5.49 μg/L h; 53.10 mL/kg, and 12.66 mL/h kg). The toxicokinetic results indicated that the hepatic first-pass effect was predominant after i.p. administration. The UPLC–Q-ToF–MS data revealed nine metabolites in plasma, urine, and bile which were largely obtained by demethylation, hydroxylation, acetylation and glycine conjugation. Metabolites were mainly excreted through urine and bile, most of which in urine was basically eliminated in 24 h. Molecular docking and liver microsome experiments further showed that gelsenicine was metabolized by cytochrome P450 3A4 and 3A5. Summarizing, the present study provides metabolic and toxicokinetic information on gelsenicine which in turn may help in future risk assessment and forensic identification after poisonings.
      PubDate: 2022-01-23
       
  • Prothioconazole induces cell cycle arrest by up-regulation of EIF4EBP1 in
           extravillous trophoblast cells

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      Abstract: Abstract Prothioconazole (PTC) is a new broad-spectrum triazole antibacterial agent that is being widely used in agriculture. PTC has been linked to a number of reproductive outcomes including embryo implantation disorder; however, the exact mechanism underlying this relationship has yet to be determined. Proper trophoblast proliferation and migration is a prerequisite for successful embryo implantation. To elucidate the underlying molecular perturbations, we detect the effect of PTC on extravillous trophoblast cells proliferation and migration, and investigate its potential mechanisms. Exposure to different concentrations of PTC (0–500 μM) significantly inhibited the cell viability and migration ability (5 μM PTC exposure), and also caused the cell cycle arrest at the lowest dose (1 μM PTC exposure). Transcriptome analysis revealed that PTC exposure disturbed multiple biological processes including cell cycle and apoptosis, consistent with cell phenotype. Specifically, eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1, 4E-BP1) was identified as up-regulated in PTC exposure group and knockdown of EIF4EBP1, and attenuated the G1 phase arrest induced by PTC exposure. In summary, our data demonstrated that 4E-BP1 participated in PTC-induced cell cycle arrest in extravillous trophoblast cells by regulating cyclin D1. These findings shed light on the potential adverse effect of PTC exposure on the embryo implantation.
      PubDate: 2022-01-20
       
  • Multi-omics analysis reveals metabolism of okadaic acid in gut lumen of
           rat

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      Abstract: Abstract Okadaic acid (OA) is an important marine lipophilic phycotoxin with various pathological properties, responsible for diarrheal shellfish poisoning events in human beings over the world. However, to date no mechanism can well explain the toxicity and symptom of OA, even diarrhea. Here, to reveal the toxic mechanism of OA to mammals, we analyzed the metabolism of OA in rat and the effects of OA exposure on the composition and function of gut bacteria using a multi-omics strategy and rRNA high-throughput technology. We found that OA exerted great effects on gut bacteria, mainly featured in heavy fluctuation of dominant genera and significant changes in the mapped bacterial function genes, including not only virulence genes of pathogenic bacteria, but also bacterial metabolism genes. In the feces of the OA-exposed group, we detected dinophysistoxin-2 (DTX-2), lespedezaflavanone F and tolytoxin, suggesting that OA could be transformed into other metabolites like DTX-2. Other metabolic biomarkers such as N-Acetyl-a-neuraminic acid, N,N-dihydroxy-l-tyrosine, nalbuphine, and coproporphyrin I and III were also highly correlated with OA content, which made the toxicity of OA more complicated and confusing. Spearman correlation test demonstrated that Bacteroides and Romboutsia were the genera most related to OA transformation, suggesting that Bacteroides and Romboutsia might play a key role in the complicated and confusing toxicity of OA. In this study, we found for the first time that OA may be converted into other metabolites in gut, especially DTX-2. This finding could not only help to reveal the complex toxicity of OA, but also have important significance for clarifying the transportation, metabolism, and environmental fate of OA in the food chain.
      PubDate: 2022-01-16
       
  • The use of Bayesian methodology in the development and validation of a
           tiered assessment approach towards prediction of rat acute oral toxicity

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      Abstract: Abstract There exists consensus that the traditional means by which safety of chemicals is assessed—namely through reliance upon apical outcomes obtained following in vivo testing—is increasingly unfit for purpose. Whilst efforts in development of suitable alternatives continue, few have achieved levels of robustness required for regulatory acceptance. An array of “new approach methodologies” (NAM) for determining toxic effect, spanning in vitro and in silico spheres, have by now emerged. It has been suggested, intuitively, that combining data obtained from across these sources might serve to enhance overall confidence in derived judgment. This concept may be formalised in the “tiered assessment” approach, whereby evidence gathered through a sequential NAM testing strategy is exploited so to infer the properties of a compound of interest. Our intention has been to provide an illustration of how such a scheme might be developed and applied within a practical setting—adopting for this purpose the endpoint of rat acute oral lethality. Bayesian statistical inference is drawn upon to enable quantification of degree of confidence that a substance might ultimately belong to one of five LD50-associated toxicity categories. Informing this is evidence acquired both from existing in silico and in vitro resources, alongside a purposely-constructed random forest model and structural alert set. Results indicate that the combination of in silico methodologies provides moderately conservative estimations of hazard, conducive for application in safety assessment, and for which levels of certainty are defined. Accordingly, scope for potential extension of approach to further toxicological endpoints is demonstrated.
      PubDate: 2022-01-16
       
  • Preliminary nonclinical safety and immunogenicity of an
           rVSV-ΔG-SARS-CoV-2-S vaccine in mice, hamsters, rabbits and pigs

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      Abstract: Abstract rVSV-ΔG-SARS-CoV-2-S is a clinical stage (Phase 2) replication competent recombinant vaccine against SARS-CoV-2. To evaluate the safety profile of the vaccine, a series of non-clinical safety, immunogenicity and efficacy studies were conducted in four animal species, using multiple doses (up to 108 Plaque Forming Units/animal) and dosing regimens. There were no treatment-related mortalities or any noticeable clinical signs in any of the studies. Compared to unvaccinated controls, hematology and biochemistry parameters were unremarkable and no adverse histopathological findings. There was no detectable viral shedding in urine, nor viral RNA detected in whole blood or serum samples seven days post vaccination. The rVSV-ΔG-SARS-CoV-2-S vaccination gave rise to neutralizing antibodies, cellular immune responses, and increased lymphocytic cellularity in the spleen germinal centers and regional lymph nodes. No evidence for neurovirulence was found in C57BL/6 immune competent mice or in highly sensitive type I interferon knock-out mice. Vaccine virus replication and distribution in K18-human Angiotensin-converting enzyme 2-transgenic mice showed a gradual clearance from the vaccination site with no vaccine virus recovered from the lungs. The nonclinical data suggest that the rVSV-ΔG-SARS-CoV-2-S vaccine is safe and immunogenic. These results supported the initiation of clinical trials, currently in Phase 2.
      PubDate: 2022-01-15
       
  • A model-based approach to designing developmental toxicology experiments
           using sea urchin embryos

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      Abstract: Abstract The key aim of this paper is to suggest a more quantitative approach to designing a dose–response experiment, and more specifically, a concentration–response experiment. The work proposes a departure from the traditional experimental design to determine a dose–response relationship in a developmental toxicology study. It is proposed that a model-based approach to determine a dose–response relationship can provide the most accurate statistical inference for the underlying parameters of interest, which may be estimating one or more model parameters or pre-specified functions of the model parameters, such as lethal dose, at maximal efficiency. When the design criterion or criteria can be determined at the onset, there are demonstrated efficiency gains using a more carefully selected model-based optimal design as opposed to an ad-hoc empirical design. As an illustration, a model-based approach was theoretically used to construct efficient designs for inference in a developmental toxicity study of sea urchin embryos exposed to trimethoprim. This study compares and contrasts the results obtained using model-based optimal designs versus an ad-hoc empirical design.
      PubDate: 2022-01-13
       
  • SUMOylation regulates the number and size of promyelocytic
           leukemia-nuclear bodies (PML-NBs) and arsenic perturbs SUMO dynamics on
           PML by insolubilizing PML in THP-1 cells

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      Abstract: Abstract The functional roles of protein modification by small ubiquitin-like modifier (SUMO) proteins are not well understood compared to ubiquitination. Promyelocytic leukemia (PML) proteins are good substrates for SUMOylation, and PML-nuclear bodies (PML-NBs) may function as a platform for the PML SUMOylation. PML proteins are rapidly modified both with SUMO2/3 and SUMO1 after exposure to arsenite (As3+) and SUMOylated PML are further ubiquitinated and degraded by proteasomes. However, effects of As3+ on SUMO dynamics on PML-NBs are not well investigated. In the present study, we report that (1) the number and size of PML-NBs were regulated by SUMO E1-activating enzyme, (2) SUMO2/3 co-localized with PML irrespective of As3+ exposure and was restricted to PML-nuclear bodies (PML-NBs) via covalent binding in response to As3+, and (3) As3+-induced biochemical changes in PML were not modulated by ubiquitin–proteasome system (UPS) in THP-1 cells. Undifferentiated and differentiated THP-1 cells responded to As3+ similarly and PML proteins were changed from the detergent soluble to the insoluble form and further SUMOylated with SUMO2/3 and SUMO1. ML792, a SUMO E1 inhibitor, decreased the number of PML-NBs and reciprocally increased the size irrespective of exposure to As3+, which itself slightly decrease both the number and size of PML-NBs. TAK243, a ubiquitin E1 inhibitor, did not change the PML-NBs, while SUMOylated proteins accumulated in the TAK243-exposed cells. Proteasome inhibitors did not change the As3+-induced SUMOylation levels of PML. Co-localization and further restriction of SUMO2/3 to PML-NBs were confirmed by PML-transfected CHO-K1 cells. Collectively, SUMOylation regulates PML-NBs and As3+ restricts SUMO dynamics on PML by changing its solubility.
      PubDate: 2022-01-10
       
  • 3D bioprinting of complex tissues in vitro: state-of-the-art and future
           perspectives

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      Abstract: Abstract The pharmacology and toxicology of a broad variety of therapies and chemicals have significantly improved with the aid of the increasing in vitro models of complex human tissues. Offering versatile and precise control over the cell population, extracellular matrix (ECM) deposition, dynamic microenvironment, and sophisticated microarchitecture, which is desired for the in vitro modeling of complex tissues, 3D bio-printing is a rapidly growing technology to be employed in the field. In this review, we will discuss the recent advancement of printing techniques and bio-ink sources, which have been spurred on by the increasing demand for modeling tactics and have facilitated the development of the refined tissue models as well as the modeling strategies, followed by a state-of-the-art update on the specialized work on cancer, heart, muscle and liver. In the end, the toxicological modeling strategies, substantial challenges, and future perspectives for 3D printed tissue models were explored.
      PubDate: 2022-01-10
       
  • Gadolinium: pharmacokinetics and toxicity in humans and laboratory animals
           following contrast agent administration

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      Abstract: Abstract Gadolinium-based contrast agents (GBCAs) have transformed magnetic resonance imaging (MRI) by facilitating the use of contrast-enhanced MRI to allow vital clinical diagnosis in a plethora of disease that would otherwise remain undetected. Although over 500 million doses have been administered worldwide, scientific research has documented the retention of gadolinium in tissues, long after exposure, and the discovery of a GBCA-associated disease termed nephrogenic systemic fibrosis, found in patients with impaired renal function. An understanding of the pharmacokinetics in humans and animals alike are pivotal to the understanding of the distribution and excretion of gadolinium and GBCAs, and ultimately their potential retention. This has been well studied in humans and more so in animals, and recently there has been a particular focus on potential toxicities associated with multiple GBCA administration. The purpose of this review is to highlight what is currently known in the literature regarding the pharmacokinetics of gadolinium in humans and animals, and any toxicity associated with GBCA use.
      PubDate: 2022-01-08
       
  • Correction to: Paradox effects of binge drinking on response inhibition
           processes depending on mental workload

    • Free pre-print version: Loading...

      PubDate: 2022-01-07
       
  • Feeding Brassica vegetables to rats leads to the formation of
           characteristic DNA adducts (from 1-methoxy-3-indolylmethyl glucosinolate)
           in many tissues

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      Abstract: Abstract Juices of Brassica vegetables are mutagenic and form characteristic DNA adducts in bacteria and mammalian cells. In this study, we examined whether such adducts are also formed in vivo in animal models. Rats fed raw broccoli ad libitum in addition to normal laboratory chow for 5 weeks showed one major adduct spot and sometimes an additional minor adduct spot in liver, kidney, lung, blood and the gastrointestinal tract, as determined by 32P-postlabelling/thin-layer chromatography. Adducts with the same chromatographic properties were formed when herring sperm DNA (or dG-3’-phosphate) was incubated with 1-methoxy-3-indolylmethyl glucosinolate (phytochemical present in Brassica plants), in the presence of myrosinase (plant enzyme that hydrolyses glucosinolates to bioactive breakdown products). UPLC–MS/MS analysis corroborated this finding: 1-Methoxy-3-indolylmethyl-substituted purine nucleosides were detected in the hepatic DNA of broccoli-fed animals, but not in control animals. Feeding raw cauliflower led to the formation of the same adducts. When steamed rather than raw broccoli was used, the adduct levels were essentially unchanged in liver and jejunum, but elevated in large intestine. Due to inactivation of myrosinase by the steaming, higher levels of the glucosinolates may have reached the large bowl to be activated by glucosidases from intestinal bacteria. In conclusion, the consumption of common Brassica vegetables can lead to the formation of substantial levels of DNA adducts in animal models. The adducts can be attributed to a specific phytochemical, neoglucobrassicin (1-methoxy-3-indolylmethyl glucosinolate).
      PubDate: 2022-01-07
       
  • Methanol-induced optic neuropathy: a still-present problem

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      Abstract: Abstract Methanol-induced optic neuropathy (Me-ION) is a serious condition that may result in long-term or irreversible visual impairment or even blindness secondary to damage and loss of function of the optic nerve and retina. Me-ION shows a tendency to occur as mass poisonings around the world with a clear predilection for poor societies in developing countries. The main mechanism underlying the molecular basis of Me-ION is the inhibition of the mitochondrial oxidative phosphorylation process through the binding of the toxic metabolite of methanol—formic acid—with the key enzyme of this process—cytochrome c oxidase. However, other mechanisms, including damage to the eye tissues by oxidative stress causing the intensification of the oxidative peroxidation process with the formation of cytotoxic compounds, as well as an increase in the synthesis of pro-inflammatory cytokines and influence on the expression of key proteins responsible for maintaining cell homeostasis, also play an important role in the pathogenesis of Me-ION. Histopathological changes in the eye tissues are mainly manifested as the degeneration of axons and glial cells of the optic nerve, often with accompanying damage of the retina that may involve all its layers. Despite the development of therapeutic approaches, persistent visual sequelae are seen in 30–40% of survivors. Thus, Me-ION continues to be an important problem for healthcare systems worldwide.
      PubDate: 2022-01-06
       
  • In vitro metabolism of helenalin and its inhibitory effect on human
           cytochrome P450 activity

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      Abstract: Abstract Sesquiterpene lactone helenalin is used as an antiphlogistic in European and Chinese folk medicine. The pharmacological activities of helenalin have been extensively investigated, yet insufficient information exists about its metabolic properties. The objectives of the present study were (1) to investigate the in vitro NADPH-dependent metabolism of helenalin (5 and 100 µM) using human and rat liver microsomes and liver cytosol, (2) to elucidate the role of human cytochrome P450 (CYP) enzymes in its oxidative metabolism, and (3) to study the inhibition of human CYPs by helenalin. Five oxidative metabolites were detected in NADPH-dependent human and rat liver microsomal incubations, while two reduced metabolites were detected only in NADPH-dependent human microsomal and cytosolic incubations. In human liver microsomes, the main oxidative metabolite was 14-hydroxyhelenalin, and in rat liver microsomes 9-hydroxyhelenalin. The overall oxidation of helenalin was several times more efficient in rat than in human liver microsomes. In humans, CYP3A4 and CYP3A5 followed by CYP2B6 were the main enzymes responsible for the hepatic metabolism of helenalin. The extrahepatic CYP2A13 oxidized helenalin most efficiently among CYP enzymes, possessing the Km value of 0.6 µM. Helenalin inhibited CYP3A4 (IC50 = 18.7 µM) and CYP3A5 (IC50 = 62.6 µM), and acted as a mechanism-based inhibitor of CYP2A13 (IC50 = 1.1 µM, KI = 6.7 µM, and kinact = 0.58 ln(%)/min). It may be concluded that the metabolism of helenalin differs between rats and humans, in the latter its oxidation is catalyzed by hepatic CYP2B6, CYP3A4, CYP3A5, and CYP3A7, and extrahepatic CYP2A13.
      PubDate: 2022-01-06
       
  • Comparing N-acetylcysteine and 4-methylpyrazole as antidotes for
           acetaminophen overdose

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      Abstract: Abstract Acetaminophen (APAP) overdose can cause hepatotoxicity and even liver failure. N-acetylcysteine (NAC) is still the only FDA-approved antidote against APAP overdose 40 years after its introduction. The standard oral or intravenous dosing regimen of NAC is highly effective for patients with moderate overdoses who present within 8 h of APAP ingestion. However, for late-presenting patients or after ingestion of very large overdoses, the efficacy of NAC is diminished. Thus, additional antidotes with an extended therapeutic window may be needed for these patients. Fomepizole (4-methylpyrazole), a clinically approved antidote against methanol and ethylene glycol poisoning, recently emerged as a promising candidate. In animal studies, fomepizole effectively prevented APAP-induced liver injury by inhibiting Cyp2E1 when treated early, and by inhibiting c-jun N-terminal kinase (JNK) and oxidant stress when treated after the metabolism phase. In addition, fomepizole treatment, unlike NAC, prevented APAP-induced kidney damage and promoted hepatic regeneration in mice. These mechanisms of protection (inhibition of Cyp2E1 and JNK) and an extended efficacy compared to NAC could be verified in primary human hepatocytes. Furthermore, the formation of oxidative metabolites was eliminated in healthy volunteers using the established treatment protocol for fomepizole in toxic alcohol and ethylene glycol poisoning. These mechanistic findings, together with the excellent safety profile after methanol and ethylene glycol poisoning and after an APAP overdose, suggest that fomepizole may be a promising antidote against APAP overdose that could be useful as adjunct treatment to NAC. Clinical trials to support this hypothesis are warranted.
      PubDate: 2022-01-03
       
  • Deoxynivalenol induces apoptosis and autophagy in human prostate
           epithelial cells via PI3K/Akt signaling pathway

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      Abstract: Abstract Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway is one of the most deregulated signaling pathway in prostate cancer. It controls basic processes in cells: cell proliferation and death. Any disturbances in the balance between cell death and survival might result in carcinogenesis. Deoxynivalenol (DON) is one of the most common mycotoxins, a toxic metabolites of fungi, present in our everyday diet and feed. Although previous studies reported DON to induce oxidative stress, modulate steroidogenesis, DNA damage and cell cycle modulation triggering together its toxicity, its effect on normal prostate epithelial cells is not known. The aim of the study was to evaluate the effect of DON on the apoptosis and autophagy in normal prostate epithelial cells via modulation of PI3K/Akt signaling pathway. The results showed that DON in a dose of 30 µM and 10 µM induces oxidative stress, DNA damage and cell cycle arrest in G2/M cell cycle phase. The higher concentration of DON induces apoptosis, whereas lower one autophagy in PNT1A cells, indicating that modulation of PI3K/Akt by DON results in the induction of autophagy triggering apoptosis in normal prostate epithelial cells.
      PubDate: 2022-01-01
       
  • Inhibitors of class I HDACs and of FLT3 combine synergistically against
           leukemia cells with mutant FLT3

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      Abstract: Abstract Acute myeloid leukemia (AML) with mutations in the FMS-like tyrosine kinase (FLT3) is a clinically unresolved problem. AML cells frequently have a dysregulated expression and activity of epigenetic modulators of the histone deacetylase (HDAC) family. Therefore, we tested whether a combined inhibition of mutant FLT3 and class I HDACs is effective against AML cells. Low nanomolar doses of the FLT3 inhibitor (FLT3i) AC220 and an inhibition of class I HDACs with nanomolar concentrations of FK228 or micromolar doses of the HDAC3 specific agent RGFP966 synergistically induce apoptosis of AML cells that carry hyperactive FLT3 with an internal tandem duplication (FLT3-ITD). This does not occur in leukemic cells with wild-type FLT3 and without FLT3, suggesting a preferential toxicity of this combination against cells with mutant FLT3. Moreover, nanomolar doses of the new FLT3i marbotinib combine favorably with FK228 against leukemic cells with FLT3-ITD. The combinatorial treatments potentiated their suppressive effects on the tyrosine phosphorylation and stability of FLT3-ITD and its downstream signaling to the kinases ERK1/ERK2 and the inducible transcription factor STAT5. The beneficial pro-apoptotic effects of FLT3i and HDACi against leukemic cells with mutant FLT3 are associated with dose- and drug-dependent alterations of cell cycle distribution and DNA damage. This is linked to a modulation of the tumor-suppressive transcription factor p53 and its target cyclin-dependent kinase inhibitor p21. While HDACi induce p21, AC220 suppresses the expression of p53 and p21. Furthermore, we show that both FLT3-ITD and class I HDAC activity promote the expression of the checkpoint kinases CHK1 and WEE1, thymidylate synthase, and the DNA repair protein RAD51 in leukemic cells. A genetic depletion of HDAC3 attenuates the expression of such proteins. Thus, class I HDACs and hyperactive FLT3 appear to be valid targets in AML cells with mutant FLT3.
      PubDate: 2022-01-01
       
  • Physiologically based kinetic modelling predicts the in vivo relative
           potency of riddelliine N-oxide compared to riddelliine in rat to be dose
           dependent

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      Abstract: Abstract Pyrrolizidine alkaloids (PAs) are toxic plant constituents occurring often in their N-oxide form. This raises the question on the relative potency (REP) values of PA-N-oxides compared to the corresponding parent PAs. The present study aims to quantify the in vivo REP value of riddelliine N-oxide compared to riddelliine using physiologically based kinetic (PBK) modelling, taking into account that the toxicity of riddelliine N-oxide depends on its conversion to riddelliine by intestinal microbiota and in the liver. The models predicted a lower Cmax and higher Tmax for the blood concentration of riddelliine upon oral administration of riddelliine N-oxide compared to the Cmax and Tmax predicted for an equimolar oral dose of riddelliine. Comparison of the area under the riddelliine concentration–time curve (AUCRID) obtained upon dosing either the N-oxide or riddelliine itself revealed a ratio of 0.67, which reflects the in vivo REP for riddelliine N-oxide compared to riddelliine, and appeared to closely match the REP value derived from available in vivo data. The models also predicted that the REP value will decrease with increasing dose level, because of saturation of riddelliine N-oxide reduction by the intestinal microbiota and of riddelliine clearance by the liver. It is concluded that PBK modeling provides a way to define in vivo REP values of PA-N-oxides as compared to their parent PAs, without a need for animal experiments.
      PubDate: 2022-01-01
       
  • Particulate and drug-induced toxicity assessed in novel quadruple cell
           human primary hepatic disease models of steatosis and pre-fibrotic NASH

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      Abstract: Abstract In an effort to replace, reduce and refine animal experimentation, there is an unmet need to advance current in vitro models that offer features with physiological relevance and enhanced predictivity of in vivo toxicological output. Hepatic toxicology is key following chemical, drug and nanomaterials (NMs) exposure, as the liver is vital in metabolic detoxification of chemicals as well as being a major site of xenobiotic accumulation (i.e., low solubility particulates). With the ever-increasing production of NMs, there is a necessity to evaluate the probability of consequential adverse effects, not only in health but also in clinically asymptomatic liver, as part of risk stratification strategies. In this study, two unique disease initiation and maintenance protocols were developed and utilised to mimic steatosis and pre-fibrotic NASH in scaffold-free 3D liver microtissues (MT) composed of primary human hepatocytes, hepatic stellate cells, Kupffer cells and sinusoidal endothelial cells. The characterized diseased MT were utilized for the toxicological assessment of a panel of xenobiotics. Highlights from the study included: 1. Clear experimental evidence for the pre-existing liver disease is important in the augmentation of xenobiotic-induced hepatotoxicity and 2. NMs are able to activate stellate cells. The data demonstrated that pre-existing disease is vital in the intensification of xenobiotic-induced liver damage. Therefore, it is imperative that all stages of the wide spectrum of liver disease are incorporated in risk assessment strategies. This is of significant consequence, as a substantial number of the general population suffer from sub-clinical liver injury without any apparent or diagnosed manifestations.
      PubDate: 2022-01-01
       
  • Organophosphorus pesticides exhibit compound specific effects in rat
           precision-cut lung slices (PCLS): mechanisms involved in airway response,
           cytotoxicity, inflammatory activation and antioxidative defense

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      Abstract: Abstract Organophosphorus compound pesticides (OP) are widely used in pest control and might be misused for terrorist attacks. Although acetylcholinesterase (AChE) inhibition is the predominant toxic mechanism, OP may induce pneumonia and formation of lung edema after poisoning and during clinical treatment as life-threatening complication. To investigate the underlying mechanisms, rat precision-cut lung slices (PCLS) were exposed to the OP parathion, malathion and their biotransformation products paraoxon and malaoxon (100–2000 µmol/L). Airway response, metabolic activity, release of LDH, cytokine expression and oxidative stress response were analyzed. A concentration-dependent inhibition of airway relaxation was observed after exposure with the oxon but not with the thion-OP. In contrast, cytotoxic effects were observed for both forms in higher concentrations. Increased cytokine expression was observed after exposure to parathion and paraoxon (IL-6, GM-CSF, MIP-1α) and IL-6 expression was dependent on NFκB activation. Intracellular GSH levels were significantly reduced by all four tested OP but an increase in GSSG and HO-1 expression was predominantly observed after malaoxon exposure. Pretreatment with the antioxidant N-acetylcysteine reduced malaoxon but not paraoxon-induced cytotoxicity. PCLS as a 3D lung model system revealed OP-induced effects depending on the particular OP. The experimental data of this study contribute to a better understanding of OP toxicity on cellular targets and may be a possible explanation for the variety of clinical outcomes induced by different OP.
      PubDate: 2022-01-01
       
  • Perspectives of future lung toxicology studies using human pluripotent
           stem cells

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      Abstract: Abstract The absence of in vitro platforms for human pulmonary toxicology studies is becoming an increasingly serious concern. The respiratory system has a dynamic mechanical structure that extends from the airways to the alveolar region. In addition, the epithelial, endothelial, stromal, and immune cells are highly organized in each region and interact with each other to function synergistically. These cells of varied lineage, particularly epithelial cells, have been difficult to use for long-term culture in vitro, thus limiting the development of useful experimental tools. This limitation has set a large distance between the bench and the bedside for analyzing the pathogenic mechanisms, the efficacy of candidate therapeutic agents, and the toxicity of compounds. Several researchers have proposed solutions to these problems by reporting on methods for generating human lung epithelial cells derived from pluripotent stem cells (PSCs). Moreover, the use of organoid culture, organ-on-a-chip, and material-based techniques have enabled the maintenance of functional PSC-derived lung epithelial cells as well as primary cells. The aforementioned technological advances have facilitated the in vitro recapitulation of genetic lung diseases and the detection of ameliorating or worsening effects of genetic and chemical interventions, thus indicating the future possibility of more sophisticated preclinical compound assessments in vitro. In this review, we will update the recent advances in lung cell culture methods, principally focusing on human PSC-derived lung epithelial organoid culture systems with the hope of their future application in toxicology studies.
      PubDate: 2022-01-01
       
 
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