Toxicology letters最新文献

{"title":"The effects of citalopram and sertraline on adipogenesis and lipogenesis in 3T3-L1 cells","authors":"Deniz Bozdag ,&nbsp;Bita Entezari ,&nbsp;Hande Gurer-Orhan","doi":"10.1016/j.toxlet.2025.02.007","DOIUrl":"10.1016/j.toxlet.2025.02.007","url":null,"abstract":"<div><div>Selective serotonin reuptake inhibitors (SSRIs), widely used antidepressants, have been associated with metabolic adverse effects, including weight gain and disrupted lipid metabolism. This study investigates the potential adipogenic and lipogenic effects of two commonly prescribed SSRIs, citalopram (CIT) and sertraline (SER), using the murine 3T3-L1 preadipocyte cell line. Key markers, such as adiponectin secretion, G3PDH activity, and the expression of critical transcription factors (PPARγ, CEBPα, SREBP1) and lipogenic enzymes (FASN, LPL), were evaluated. Furthermore, assessment of intracellular lipid accumulation via Oil Red O staining was used as a measure for enhanced adipogenesis. The results show that CIT significantly increased adiponectin secretion and G3PDH activity, with comparable potency to the positive control, rosiglitazone. Both SSRIs upregulated the transcription of key adipogenic genes but displayed discrepancies in protein expression. Despite these molecular changes, neither CIT nor SER promoted lipid accumulation, indicating disruption of adipogenic and lipogenic processes without direct stimulation of fat storage. These findings underscore the complexity of SSRI-induced metabolic effects and the need for further studies to evaluate their long-term impact.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"405 ","pages":"Pages 67-75"},"PeriodicalIF":2.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aristolochic acid-induced DNA adduct formation triggers acute DNA damage response in rat kidney proximal tubular cells","authors":"Miyu Komatsu,&nbsp;Takeshi Funakoshi,&nbsp;Toshihiko Aki,&nbsp;Kana Unuma","doi":"10.1016/j.toxlet.2025.02.006","DOIUrl":"10.1016/j.toxlet.2025.02.006","url":null,"abstract":"<div><div>Aristolochic acid nephropathy (AAN) is a form of acute kidney injury triggered by the ingestion of aristolochic acid (AA), characterized by significant degeneration and loss of cells in the proximal tubules. Previous reports of AA-induced acute kidney injury have reported that AA-induced cytotoxicity can occur within a short period, up to 24 h; however, there are few reports on the relationship between AA-DNA adduct formation and cytotoxic mechanism during the acute phase. In this study, we aimed to elucidate the toxicological mechanisms in the initial phase of AA exposure by examining the effects of AA on NRK-52E rat proximal tubular cells within 24 h. We detected the formation of AA-DNA adducts as early as 4 h post-exposure, indicating that 50 μM of AA causes DNA damage. The DNA damage response pathway was activated, peaking at 8 h post-exposure. Additionally, we observed an increasing trend of G1 phase cell cycle arrest after 8 h, followed by a significant decline in cell viability at 16 h. These findings suggest that 50 μM of AA induces rapid DNA damage in NRK-52E cells, primarily through the formation of AA-DNA adducts, ultimately leading to G1 phase cell cycle arrest.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"406 ","pages":"Pages 1-8"},"PeriodicalIF":2.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurotoxic implications of gliotoxin and ochratoxin A in SH-SY5Y cells: ROS-induced apoptosis and genotoxicity","authors":"Raquel Penalva-Olcina,&nbsp;Cristina Juan,&nbsp;Mónica Fernández-Franzón,&nbsp;Ana Juan-García","doi":"10.1016/j.toxlet.2025.02.004","DOIUrl":"10.1016/j.toxlet.2025.02.004","url":null,"abstract":"<div><div>Gliotoxin (GTX) and ochratoxin A (OTA) are naturally produced toxins by fungi and are known for their potential health risks. With the aim of shed some light on the mechanisms by which GTX, OTA, and their combination exert toxicity at neuronal level, the following <em>in vitro</em> studies were conducted in SH-SY5Y cells: a) intracellular ROS monitorization by the H2-DCFDA assay b) study of the expression of pro-apoptotic genes <em>Bcl2, Casp-3</em>, and <em>Bax</em> by RT-qPCR c) study of the apoptotic-necrotic progression of SH-SY5Y cells by flow cytometry; d) study of the genotoxic potential through the <em>in vitro</em> micronucleus (MN) assay also by flow cytometry following OECD TG 487 guidelines. ROS production was increased when cells were exposed to mycotoxins at all scenarios tested highlighting the effects of GTX. Regarding gene expression, increases of <em>Bax</em> and <em>Casp-3</em> genes at 1.3- and 3- folds respectively were observed when cells were exposed to GTX at 0.75 μM, with a more prominent increase after exposure to the binary combination [GTX + OTA] at [0.2 + 0.1] µM, increasing 3 and 5-folds more, respectively when compared to the control. MN formation increased a 30 % compared to control when exposed to GTX at 0.4 μM, 43 % for OTA at 0.8 μM, with the highest increase observed when cells were exposed to the combination [GTX + OTA] at [0.2 + 1.5] μM, obtaining a 65 % more MN formation. Based on the results obtained, we can conclude that for the proposed scenarios of exposure to GTX, OTA, and their combination, genotoxic effects together with oxidative effects at neuronal level in SH-SY5Y cell line, were found to play a key role in their mechanisms of toxic action.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"405 ","pages":"Pages 51-58"},"PeriodicalIF":2.9,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicological mode-of-action and developmental toxicity of different carbon chain length PFAS","authors":"Kamlesh Sodani ,&nbsp;Bas Ter Braak ,&nbsp;Sabine Hartvelt ,&nbsp;Mark Boelens ,&nbsp;Amer Jamalpoor ,&nbsp;Sandeep Mukhi","doi":"10.1016/j.toxlet.2025.02.003","DOIUrl":"10.1016/j.toxlet.2025.02.003","url":null,"abstract":"<div><div>Per-and polyfluoro alkyl substances (PFAS), also known as “forever chemicals”, are deemed as highly toxic with similar toxicological mode-of-action (MoA) and potency. However, varying carbon chain length and functional head-group of PFAS can affect their physicochemical properties, resulting in different toxicological properties. To assess PFAS toxicological MoA and to distinguish between high toxic PFAS and the low-toxic analogs, we tested a set of eight PFAS with varying carbon chain length (C2-C10) in the ToxProfiler assay. ToxProfiler is a human <em>in vitro</em> assay containing seven fluorescent reporters to visualize and quantify activation of the major cellular stress pathways: oxidative stress, cell cycle stress, endoplasmic reticulum (ER) stress, autophagy, ion stress, protein stress and inflammation. In addition, we evaluated teratogenicity potential of long-chain PFAS perfluorooctanoic acid (PFOA; C8), and the ultrashort-chain PFAS trifluoroacetic acid (TFA; C2) in ReproTracker, a human induced pluripotent stem cell (hiPSCs)-based assay in which differentiation into cardiomyocytes, hepatocytes, and neural rosettes is followed to identify developmental toxicity hazards of new drugs and chemicals. In this study, we identified long-chain PFAS (C8-C10), such as PFOA (C8) to be more cytotoxic than ultrashort-chain PFAS and to predominantly induce ER and oxidative stress at 130 µM. PFAS with a carbon chain length of C4-C7 primarily induced autophagy (300 µM) in ToxProfiler. Ultrashort-chain PFAS trifluoroacetic acid (TFA; C2) and perfluoropropionic acid (PFPrA; C3) did not activate any of the ToxProfiler stress response reporters and were not cytotoxic at their maximum tested concentrations (10 mM). In concordance, exposure of differentiating cells to PFOA in ReproTracker led to a concentration-dependent decrease in the hepatocyte-specific and neuroectodermal biomarker genes and disrupted their morphology at 30 and 60 µM, respectively. TFA had no significant effect on biomarker expression, nor on the morphology/functionality of the three differentiated cells. Altogether, we demonstrated that the carbon chain length of PFAS can determine their <em>in vitro</em> toxicity and ultrashort-chain PFAS (TFA) were found to be less toxic when compared to long-chain PFAS.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"405 ","pages":"Pages 59-66"},"PeriodicalIF":2.9,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low doses of bisphenol F and S affect human ovarian granulosa cells by reducing the number of active mitochondria and ATP synthesis","authors":"Paulina Głód ,&nbsp;Weronika Marynowicz ,&nbsp;Joanna Homa ,&nbsp;Joanna Smoleniec ,&nbsp;Dawid Maduzia ,&nbsp;Anna Ptak","doi":"10.1016/j.toxlet.2025.02.002","DOIUrl":"10.1016/j.toxlet.2025.02.002","url":null,"abstract":"<div><div>Bisphenols (BPs) are a group of environmental pollutants mainly represented by bisphenol S (BPS) and F (BPF). In ovaries, BPs can accumulate in follicular fluid (FF), changing the follicular microenvironment and simultaneously affecting ovarian granulosa cells (GCs) function. In the present study, we determined the effects of BPS and BPF on oxidative stress and mitochondrial function in human ovarian GCs. Single, short-term treatment with BPs at doses reflecting their concentrations in FF (10 nM) did not affect reactive oxygen species (ROS) levels but induced mitochondrial membrane depolarization. BPF-induced mitophagy decreased the number of active mitochondria and consequently reduced the ATP production rate. The observed changes did not translate into lowered viability of GCs, but long-term treatment with BPF influenced the intrinsic apoptosis pathway by increasing caspase 9 activity without affecting apoptosis. GCs are crucial for ovarian function as they produce primary steroid hormones and regulate oocyte maturation and follicle growth. Mitochondrial dysfunction caused by BPs, manifesting as reduced ATP production in GCs, can directly cause ovarian disorders such as infertility. Therefore, this study highlights the significance of investigating the effects of BPs on reproductive health.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"405 ","pages":"Pages 41-50"},"PeriodicalIF":2.9,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The herbicide 2,4-dichlorophenoxyacetic acid induces pancreatic β-cell death via oxidative stress-activated AMPKα signal downstream-regulated apoptotic pathway","authors":"Ken-An Lin ,&nbsp;Chin-Chuan Su ,&nbsp;Kuan-I Lee ,&nbsp;Shing-Hwa Liu ,&nbsp;Kai-Min Fang ,&nbsp;Chih-Hsin Tang ,&nbsp;Wei-Cheng Lia ,&nbsp;Chun-Ying Kuo ,&nbsp;Kai-Chih Chang ,&nbsp;Chun-Fa Huang ,&nbsp;Ya-Wen Chen ,&nbsp;Ching-Yao Yang","doi":"10.1016/j.toxlet.2025.01.009","DOIUrl":"10.1016/j.toxlet.2025.01.009","url":null,"abstract":"<div><div>2,4-Dichlorophenoxyacetic acid (2,4-D) is one of commonly and widely used organic herbicides in agriculture. It has been reported that 2,4-D can induce adverse effects in mammalian cells. Epidemiological and animal studies have indicated that exposure to 2,4-D is associated with poorer glycemic control and impaired pancreatic β-cell function. However, limited information is available on 2,4-D-induced toxicological effects in β-cells, with the underlying toxicological mechanisms remains unclear. Herein, our results showed that 2,4-D exposure (30–500 μg/mL) significantly reduced cell viability, induced mitochondria dysfunction (including the mitochondrial membrane potential (MMP) loss, the increase in cytosolic cytochrome c release, and the change in Bcl-2 and Bax protein expression), and triggered apoptotic events (including the increased population of apoptotic cells, caspase-3 activity, and caspase-3/-7 and PAPR activation) in RIN-m5F β-cells, accompanied with insulin secretion inhibition. Exposure of cells to 2,4-D could also evoke JNK, ERK1/2, p38, and AMP-activated protein kinase (AMPK)α activation as well as reactive oxygen species (ROS) generation. Pretreatment of cells with compound C (an AMPK inhibitor) and the antioxidant<em>N</em>-acetylcysteine (NAC), but not that SP600125/PD98059/SB203580 (the inhibitors of JNK/ERK/p38, respectively), obviously attenuated the 2,4-D-triggered AMPKα phosphorylation, MMP loss, apoptotic events, and insulin secretion dysfunction,as similar effects with the transfection with AMPKα1-specific siRNA. Of note, buffering the ROS production with NAC obviously prevented the 2,4-D-induced ROS generation as well as AMPKα activation, but the either compound C and AMPKα1-specific siRNA transfection could not effectively reduce 2,4-D-induced ROS generation. Collectively, these findings indicate that the induction of oxidative stress-activated AMPKα signaling is a crucial mechanism underlying 2,4-D-triggered mitochondria-dependent apoptosis, ultimately leading to β-cell death.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"405 ","pages":"Pages 16-29"},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitigation of gentamycin induced acute kidney injury due to benzothiazole derivatives N1 and N5: Antioxidant and renoprotective mechanisms in-vivo zebrafish","authors":"S. Madesh ,&nbsp;Senthilkumar Palaniappan ,&nbsp;Anand Aravind ,&nbsp;Avra Sau ,&nbsp;Mikhlid H. Almutairi ,&nbsp;Bader O. Almutairi ,&nbsp;Ilavenil Soundharrajan ,&nbsp;S. Karthick Raja Namasivayam ,&nbsp;Kathiravan Muthu Kumaradoss ,&nbsp;Jesu Arockiaraj","doi":"10.1016/j.toxlet.2025.02.001","DOIUrl":"10.1016/j.toxlet.2025.02.001","url":null,"abstract":"<div><div>Acute kidney injury (AKI) is marked by a rapid decline in renal function, often caused by oxidative stress and nephrotoxic agents. Complications limit current therapeutic strategies, and no specific drugs are available to prevent renal injury or accelerate recovery. In the present research, we investigated the therapeutic efficacy of synthesized 2-aminobenzothiazole derivatives, N1 and N5, in mitigating Gentamicin (Gen) -induced renal damage <em>in vivo</em> zebrafish. The preliminary work of radical scavenging and hemolysis inhibition assay revealed that, both compounds exhibited strong antioxidant and anti-inflammatory activities. Furthermore, acute toxicity assays in zebrafish embryo/larvae revealed no adverse effects at concentrations up to 200 μM were tested, highlighting the safety of these compounds. In the zebrafish AKI model, Gen exposure led to oxidative stress, inflammation, and impaired glomerular filtration with tissue damage. Treatment with N1 and N5 significantly reduced ROS levels, apoptosis, and lipid peroxidation and restored antioxidant enzyme activities. Furthermore, N5 treatment improved renal filtration and reduced proteinuria levels, indicating its ability to mitigate nephrotoxic effects. Gene expression analysis showed that N1 and N5 downregulated pro-inflammatory markers (<em>cox-2</em>, <em>tnfα</em>, <em>mpo</em>) and angiogenic mediators (<em>vegf</em>, <em>vegfr2</em>), demonstrating anti-inflammatory and anti-angiogenic properties. Histological analyses revealed that N1 and N5 attenuated glomerular and tubular damage, reduced necrosis, and promoted tissue repair. These findings highlight the potential of 2-aminothiazole derivatives as effective therapeutic agents for AKI, offering antioxidant, anti-inflammatory, and cytoprotective benefits and warranting further investigation into their long-term efficacy in chronic kidney disease models.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"405 ","pages":"Pages 30-40"},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional profiling of exosomes derived from serum of patients with rare earth pneumoconiosis by RNA-sequencing and PI3K/Akt pathway is activated in lung of mice exposed to rare earth Nd2O3","authors":"Yanrong Gao ,&nbsp;Shurui Wang ,&nbsp;Yuanqi He ,&nbsp;Yupeng Ma ,&nbsp;Suhua Wang","doi":"10.1016/j.toxlet.2025.01.001","DOIUrl":"10.1016/j.toxlet.2025.01.001","url":null,"abstract":"<div><div>Rare earth is used extensively around the world, and rare earth particles cause a respiratory disease in workers termed rare earth pneumoconiosis(REP) that have attracted considerable attention. However, the mechanisms of REP, characterized by diffuse pulmonary fibrosis, are elusive. REP progression involves various signaling pathway networks comprising numerous cell types and cytokines. Acting as an important medium for communication between cells, exosomes are emerging as a major research topic. However, the role of exosomal lncRNAs, miRNAs and mRNAs in REP remains unclear. In the present study, we conducted high-throughput RNA sequencing to generate long non-coding RNA(lncRNA), microRNA (miRNA) and mRNA profiles from the serum exosomes of nine patients with rare earth pneumoconiosis and nine healthy people. Our results identified a total of 94 lncRNAs, 93miRNAs, and 29 mRNAs were differentially expressed in the serum exosomes of patients with rare earth pneumoconiosis. Subsequently, Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to analyze the differentially expressed RNAs. The abundant enriched GO terms of exosomal genes are cytoplasm, protein binding, cytoskeleton, Nuclear cytoplasmic transport, and KEGG pathways of exosomal genes included metabolic and cancer pathway, PI3K/Akt, wnt, mTOR, HIF-1, actin cytoskeleton and cell cycle and so on. RT-qPCR results showed that lnc-KCNMB2-AS1, hsa-miR-186–5p, hsa-miR-100–5p, hsa-miR-381–5p, NCOA4 and PLXDC1 were up-regulated, and lnc-TMEM151A, hsa-miR-758–5p and hsa-miR-6842–5p were significantly down-regulated in exosomes. In addition, our study fuond that the PI3K/Akt pathway was activated, and the expression level of miR-100–5p was increased synchronously in lung tissue of mice exposed to rare earth Nd₂O₃. In this study, PI3K/Akt pathway is significant helpful in elucidating the mechanism of REP. These findings can provide new insights into the mechanism of REP and develop a novel treatment strategy and biomarker.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"404 ","pages":"Pages 9-19"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Review of the genotoxicity of \"Arvin compounds\", drinking water contaminants formed by the degradation of antioxidants in polyolefin pipes” [Toxicol. Lett. 402 (2024) 81–90]","authors":"Wolfgang Dekant","doi":"10.1016/j.toxlet.2025.01.006","DOIUrl":"10.1016/j.toxlet.2025.01.006","url":null,"abstract":"","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"404 ","pages":"Page 67"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A simple acetylcholinesterase inhibition assay for the quantification of the nerve agent VX: Application in a Franz cell model with rat skin and various decontaminants","authors":"Amelie Schwab ,&nbsp;Gabriele Horn ,&nbsp;Kai Kehe ,&nbsp;Franz Worek ,&nbsp;Niko Amend","doi":"10.1016/j.toxlet.2025.01.002","DOIUrl":"10.1016/j.toxlet.2025.01.002","url":null,"abstract":"<div><div>The medical community continues to regard organophosphate nerve agent poisoning as a significant concern. Due to the lack of therapeutic options for the nicotinic signs and symptoms for certain agents (e.g. tabun), decontamination remains a pivotal aspect of patient care. Current models to study skin penetration of nerve agents and the respective decontamination rely on expensive, laborious and not readily available methods, i.e. GC-MS-MS and LC-MS-MS. Hence, we used a photometric acetylcholinesterase (AChE) inhibition assay for the quantification of nerve agents, relying on VX as a model substance. Inhibition curves were determined in a time dependent manner and consecutively slopes of the tangents and the calculated standard curve were used for quantification. The concentration dependent rate constant of VX with human AChE (<em>k</em>_<em>1</em>) and the inhibitor concentration [IX] were used to plot 1/<em>k</em>_<em>1</em> against 1/[IX]-(1-<em>α</em>). <em>α</em> equals [S]/(<em>K</em>_<em>m</em>+[S]), [S] being the substrate and K_m the Michaelis-Menten-constant. A Franz cell model served as an example to determine the robustness and suitability of the assay to study penetration rates and the success of decontamination. The inhibition assay delivers robust results, even when the decontamination protocol interferes with the colorimetric Ellman assay. Hence, we provide a generic, low-cost method for the quantification of nerve agents in a model studying the decontamination of nerve agents.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"404 ","pages":"Pages 20-27"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}