Modular air-liquid interface aerosol exposure system (MALIES) to study toxicity of nanoparticle aerosols in 3D-cultured A549 cells in vitro
We present a novel lung aerosol exposure system named MALIES (modular air-liquid interface exposure system), which allows three-dimensional cultivation of lung epithelial cells in alveolar-like scaffolds (MatriGrids®) and exposure to nanoparticle aerosols. MALIES consists of multiple modular units for aerosol generation, and can be rapidly assembled and commissioned. The MALIES system was proven for its ability to reliably produce a dose-dependent toxicity in A549 cells using CuSO4 aerosol. Cytotoxic effects of BaSO4- and TiO2-nanoparticles were investigated using MALIES with the human lung tumor cell line A549 cultured a...
Source: Archives of Toxicology - February 10, 2024 Category: Toxicology Authors: M J K üstner D Eckstein D Brauer P Mai J Hampl F Weise B Schuhmann G Hause F Glahn H Foth A Schober Source Type: research
Investigating the applicability domain of the hiPSC-based PluriLum assay: an embryotoxicity assessment of chemicals and drugs
Arch Toxicol. 2024 Feb 4. doi: 10.1007/s00204-023-03675-1. Online ahead of print.ABSTRACTTo meet the growing demand for developmental toxicity assessment of chemicals, New Approach Methodologies (NAMs) are needed. Previously, we developed two 3D in vitro assays based on human-induced pluripotent stem cells (hiPSC) and cardiomyocyte differentiation: the PluriBeat assay, based on assessment of beating differentiated embryoid bodies, and the PluriLum assay, a reporter gene assay based on the expression of the early cardiac marker NKX2.5; both promising assays for predicting embryotoxic effects of chemicals and drugs. In this ...
Source: Archives of Toxicology - February 4, 2024 Category: Toxicology Authors: Andreas Frederik Treschow Maria Jo ão Valente Karin Lauschke Bj ørn Holst Anders Reenberg Andersen Anne Marie Vinggaard Source Type: research
Cardiovascular responses of adult male Sprague-Dawley rats following acute organophosphate intoxication and post-exposure treatment with midazolam with or without allopregnanolone
Arch Toxicol. 2024 Feb 2. doi: 10.1007/s00204-023-03679-x. Online ahead of print.ABSTRACTRecent experimental evidence suggests combined treatment with midazolam and allopregnanolone is more effective than midazolam alone in terminating seizures triggered by acute organophosphate (OP) intoxication. However, there are concerns that combined midazolam and allopregnanolone increases risk of adverse cardiovascular events. To address this, we used telemetry devices to record cardiovascular responses in adult male Sprague-Dawley rats acutely intoxicated with diisopropylfluorophosphate (DFP). Animals were administered DFP (4 mg/kg...
Source: Archives of Toxicology - February 2, 2024 Category: Toxicology Authors: Shiyue Pan Donald A Bruun Pamela J Lein Chao-Yin Chen Source Type: research
Distinct concentration-dependent oxidative stress profiles by cadmium in a rat kidney proximal tubule cell line
Arch Toxicol. 2024 Jan 30. doi: 10.1007/s00204-023-03677-z. Online ahead of print.ABSTRACTLevels and chemical species of reactive oxygen/nitrogen species (ROS/RNS) determine oxidative eustress and distress. Abundance of uptake pathways and high oxygen consumption for ATP-dependent transport makes the renal proximal tubule particularly susceptible to cadmium (Cd2+)-induced oxidative stress by targeting ROS/RNS generation or antioxidant defence mechanisms, such as superoxide dismutase (SOD) or H2O2-metabolizing catalase (CAT). Though ROS/RNS are well-evidenced, the role of distinct ROS profiles in Cd2+ concentration-dependen...
Source: Archives of Toxicology - January 30, 2024 Category: Toxicology Authors: Wing-Kee Lee Stephanie Probst Bettina Scharner Timo Deba Faouzi Dahdouh Frank Th évenod Source Type: research
Molecular signatures of angiogenesis inhibitors: a single-embryo untargeted metabolomics approach in zebrafish
Arch Toxicol. 2024 Mar;98(3):943-956. doi: 10.1007/s00204-023-03655-5. Epub 2024 Jan 29.ABSTRACTAngiogenesis is a key process in embryonic development, a disruption of this process can lead to severe developmental defects, such as limb malformations. The identification of molecular perturbations representative of antiangiogenesis in zebrafish embryo (ZFE) may guide the assessment of developmental toxicity from an endpoint- to a mechanism-based approach, thereby improving the extrapolation of findings to humans. Thus, the aim of the study was to discover molecular changes characteristic of antiangiogenesis and developmental...
Source: Archives of Toxicology - January 29, 2024 Category: Toxicology Authors: Pia Wilhelmi Volker Haake Franziska M Zickgraf Varun Giri Philipp Ternes Peter Driemert Julia N öth Stefan Scholz Marta Barenys Burkhard Flick Barbara Birk Hennicke Kamp Robert Landsiedel Dorothee Funk-Weyer Source Type: research
Utility of in vivo metabolomics to support read-across for UVCB substances under REACH
Arch Toxicol. 2024 Mar;98(3):755-768. doi: 10.1007/s00204-023-03638-6. Epub 2024 Jan 24.ABSTRACTStructure-based grouping of chemicals for targeted testing and read-across is an efficient way to reduce resources and animal usage. For substances of unknown or variable composition, complex reaction products, or biological materials (UVCBs), structure-based grouping is virtually impossible. Biology-based approaches such as metabolomics could provide a solution. Here, 15 steam-cracked distillates, registered in the EU through the Lower Olefins Aromatics Reach Consortium (LOA), as well as six of the major substance constituents,...
Source: Archives of Toxicology - January 24, 2024 Category: Toxicology Authors: H Kamp N Aygun Kocabas F Faulhammer N Synhaeve E Rushton B Flick V Giri S Sperber L G Higgins M G Penman B van Ravenzwaay M Rooseboom Source Type: research
Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases
This article provides an overview of the background knowledge of ferroptosis in the nervous system, as well as the key role of nuclear factor E2-related factor 2 (Nrf2) in regulating ferroptosis. The article takes Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) as the starting point to explore the close association between Nrf2 and ferroptosis, which is of clear and significant importance for understanding the mechanism of neurodegenerative diseases (NDs) based on oxidative stress (OS). Accumulating evidence links ferroptosis to the pathogenesis of NDs....
Source: Archives of Toxicology - January 24, 2024 Category: Toxicology Authors: Yao Xiang Xiaohua Song Dingxin Long Source Type: research
The phosphylated butyrylcholinesterase-derived tetrapeptide GlyGluSerAla proves exposure to organophosphorus agents with enantioselectivity
Arch Toxicol. 2024 Mar;98(3):791-806. doi: 10.1007/s00204-023-03657-3. Epub 2024 Jan 24.ABSTRACTWe herein present for the first time the phosphylated (*) tetrapeptide (TP)-adduct GlyGluSer198*Ala generated from butyrylcholinesterase (BChE) with proteinase K excellently suited for the verification of exposure to toxic organophosphorus nerve agents (OPNA). Verification requires bioanalytical methods mandatory for toxicological and legal reasons. OPNA react with BChE by phosphonylation of the active site serine residue (Ser198) forming one of the major target protein adducts for verification. After its enzymatic cleavage with...
Source: Archives of Toxicology - January 24, 2024 Category: Toxicology Authors: Tamara Kranawetvogl Markus Siegert Dirk Steinritz Horst Thiermann Harald John Source Type: research
The cytotoxicity of microcystin-LR: ultrastructural and functional damage of cells
Arch Toxicol. 2024 Mar;98(3):663-687. doi: 10.1007/s00204-023-03676-0. Epub 2024 Jan 22.ABSTRACTMicrocystin-LR (MC-LR) is a toxin produced by cyanobacteria, which is widely distributed in eutrophic water bodies and has multi-organ toxicity. Previous cytotoxicity studies have mostly elucidated the effects of MC-LR on intracellular-related factors, proteins, and DNA at the molecular level. However, there have been few studies on the adverse effects of MC-LR on cell ultrastructure and function. Therefore, research on the cytotoxicity of MC-LR in recent years was collected and summarized. It was found that MC-LR can induce a s...
Source: Archives of Toxicology - January 22, 2024 Category: Toxicology Authors: Kangfeng Ge Xingde Du Haohao Liu Ruiyang Meng Chunrui Wu Zongxin Zhang Xiao Liang Jun Yang Huizhen Zhang Source Type: research
Sex differences in the tumor promoting effects of tobacco smoke in a cRaf transgenic lung cancer disease model
Arch Toxicol. 2024 Mar;98(3):957-983. doi: 10.1007/s00204-023-03671-5. Epub 2024 Jan 21.ABSTRACTTobacco smoke (TS) is the leading cause for lung cancer (LC), and female smokers are at a greater risk for LC. Yet, the underlying causes are unknown. We performed whole genome scans in TS exposed wild type and histologically characterized tumor lesions of cRaf transgenic mice. We constructed miRNA-gene and transcription factor-miRNA/gene regulatory networks and determined sex-specific gene regulations by evaluating hormone receptor activities. We validated the findings from TS exposed cRaf mice in a large cohort of smoking and ...
Source: Archives of Toxicology - January 21, 2024 Category: Toxicology Authors: Shen Zhong J ürgen Borlak Source Type: research
Sex-related differences in delayed doxorubicin-induced cardiac dysfunction in C57BL/6 mice
Arch Toxicol. 2024 Jan 20. doi: 10.1007/s00204-023-03678-y. Online ahead of print.ABSTRACTCancer survivors may experience long-term cardiovascular complications due to chemotherapeutic drugs such as doxorubicin (DOX). The exact mechanism of delayed DOX-induced cardiotoxicity has not been fully elucidated. Sex is an important risk factor for DOX-induced cardiotoxicity. In the current study, we identified sex differences in delayed DOX-induced cardiotoxicity and determined the underlying molecular determinants of the observed sexual dimorphism. Five-week-old male and female mice were administered intraperitoneal injections o...
Source: Archives of Toxicology - January 20, 2024 Category: Toxicology Authors: Ibrahim Y Abdelgawad Benu George Marianne K O Grant Yingbo Huang Yuting Shan R Stephanie Huang Beshay N Zordoky Source Type: research
Artificial intelligence (AI)-it's the end of the tox as we know it (and I feel fine)
Arch Toxicol. 2024 Mar;98(3):735-754. doi: 10.1007/s00204-023-03666-2. Epub 2024 Jan 20.ABSTRACTThe rapid progress of AI impacts diverse scientific disciplines, including toxicology, and has the potential to transform chemical safety evaluation. Toxicology has evolved from an empirical science focused on observing apical outcomes of chemical exposure, to a data-rich field ripe for AI integration. The volume, variety and velocity of toxicological data from legacy studies, literature, high-throughput assays, sensor technologies and omics approaches create opportunities but also complexities that AI can help address. In parti...
Source: Archives of Toxicology - January 20, 2024 Category: Toxicology Authors: Nicole Kleinstreuer Thomas Hartung Source Type: research
Exposure limits for indoor volatile substances concerning the general population: The role of population-based differences in sensory irritation of the eyes and airways for assessment factors
Arch Toxicol. 2024 Mar;98(3):617-662. doi: 10.1007/s00204-023-03642-w. Epub 2024 Jan 19.ABSTRACTAssessment factors (AFs) are essential in the derivation of occupational exposure limits (OELs) and indoor air quality guidelines. The factors shall accommodate differences in sensitivity between subgroups, i.e., workers, healthy and sick people, and occupational exposure versus life-long exposure for the general population. Derivation of AFs itself is based on empirical knowledge from human and animal exposure studies with immanent uncertainty in the empirical evidence due to knowledge gaps and experimental reliability. Sensory...
Source: Archives of Toxicology - January 19, 2024 Category: Toxicology Authors: Stefan Kleinbeck Peder Wolkoff Source Type: research
Probing the hair detectability of prohibited substances in sports: an in vivo-in silico-clinical approach and analytical implications compared with plasma, urine, and faeces
This study systematically assessed the detectability of prohibited substances in sports using a multifaceted approach. Initially, an animal model received a subset of 17 model drugs to compare dose dependencies and detection windows across different matrices. Subsequently, hair incorporation data from the animal experiment were extrapolated to all substances on the World Anti-Doping Agency's List through in-silico prediction. The detectability of substances in hair was further validated in a proof-of-concept human study involving the consumption of diuretics and masking agents. Semi-quantitative analysis of substances in s...
Source: Archives of Toxicology - January 15, 2024 Category: Toxicology Authors: Shao-Hsin Hung Hung-Lin Kan Chun-Wei Tung Yi-Ching Lin Ting-Ting Chen Ciao Tian William Chih-Wei Chang Source Type: research
Quantitative determination of the intracellular uptake of silica nanoparticles using asymmetric flow field flow fractionation coupled with ICP mass spectrometry and their cytotoxicity in HepG2 cells
Arch Toxicol. 2024 Mar;98(3):769-777. doi: 10.1007/s00204-023-03672-4. Epub 2024 Jan 14.ABSTRACTWe established a size separation method for silica nanoparticles (SiNPs) measuring 10, 30, 50, 70, and 100 nm in diameter using asymmetric flow field flow fractionation hyphenated with inductively coupled plasma mass spectrometry (AF4-ICP-MS), and evaluated the cytotoxicity of SiNPs in human hepatoma HepG2 cells. Analysis of the mixture sample revealed that nanoparticles of different sizes were eluted at approximately 2-min intervals, with no effect on each elution time or percentage recovery. Compared with larger SiNPs, smaller...
Source: Archives of Toxicology - January 14, 2024 Category: Toxicology Authors: Yu-Ki Tanaka Yasumitsu Ogra Source Type: research
