Toxicology最新文献

{"title":"The correlation between lung surfactant function inhibition in vitro and the effect on breathing of mice during inhalation exposure – A study of spray-formulated engine/brake cleaners and lubricating products","authors":"Jorid B. Sørli ,&nbsp;Sreyoshee Roy Sengupta ,&nbsp;Niels Hadrup","doi":"10.1016/j.tox.2025.154287","DOIUrl":"10.1016/j.tox.2025.154287","url":null,"abstract":"<div><div>Moving parts in motors require maintenance, both lubrication for smooth operation and de-greasing for cleaning and repair. Since these motor parts are hard to reach, cleaning and lubrication products are often applied by spraying. However, the aerosol spray of the product can potentially reach the breathing zone of the worker and end up in the lungs. We investigated eight products and two single ingredients for their acute effects on the lungs. The effects of the aerosolized substances were tested in an in vitro model for lung surfactant function inhibition. The in vitro results were then compared to the effects of the aerosolized substances on the breathing parameters of exposed mice, measured in whole-body plethysmographs. No-observed-adverse–effect-concentrations were set based on the endpoint of reduction in tidal volume. When a reduction in tidal volume was used as the ´true´ result, the in vitro test for lung surfactant inhibition was 80 % accurate at predicting if the substance affected tidal volume in exposed mice. The ranking of test substances were similar between the in vivo and in vitro results with the exception of (2-methoxymethylethoxy)propanol (substance A). This substance did not inhibit lung surfactant function, but was potent at reducing tidal volume in mice. In conclusion, lung surfactant function inhibition in vitro can be used as a screening tool for acute effects of ingredients in- or formulated -spray products on the lungs.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"519 ","pages":"Article 154287"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193119","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":"Microplastics and nanoplastics, emerging pollutants, increased the risk of pulmonary fibrosis in vivo and in vitro: A comparative evaluation of their potential toxicity effects with different polymers and size","authors":"Jia-Yi Dou ,&nbsp;Sen Liu ,&nbsp;Chen-Yu Wang ,&nbsp;Xu Dai ,&nbsp;Li-Hua Lian ,&nbsp;Zhen-Yu Cui ,&nbsp;Ji-Xing Nan ,&nbsp;Yan-Ling Wu","doi":"10.1016/j.tox.2025.154304","DOIUrl":"10.1016/j.tox.2025.154304","url":null,"abstract":"<div><div>With the increasing consumption of plastic products, microplastics (MPs) and nanoplastics (NPs), as new environmental pollution, pose a huge potential threat to human health. The different polymers and sizes of MPs and NPs are important factors determining the distribution and pathways of particulate organisms, thereby affecting their toxicity. The study explored the pulmonary toxicity and potential mechanism of MPs (1 μm) and NPs (100 nm) of polystyrene (PS), polyethylene (PE), or polypropylene (PP) <em>in vivo</em> and <em>in vitro</em>. Intratracheal injection of MPs/NPs (10 mg/kg, once every six days, continued four times) in mice induced pulmonary histopathological changes, raised α-SMA and collagen I expressions, the TIMP-1/MMP13 ratio, epithelial-mesenchymal transition (EMT)-related proteins, recruited immune cells and increased pro-inflammatory cytokine secretion, especially in PS-NPs group. MPs/NPs (PS, PE or PP) exhibited cytotoxicity in human lung epithelial BEAS-2B, and MPs/NPs (50 μg/mL, 8 h) up-regulated α-SMA, Vimentin, and IL-1β expressions. PS-NPs raised YAP1 and inhibited FXR expression in mice or BEAS-2B, compared with other polymers or diameters. In PS-NPs-induced BEAS-2B, Verteporfin (YAP1 antagonist, 0.2 μM) or GW4064 (FXR agonist, 2 μM) reduced α-SMA, Vimentin, and IL-1β expressions, while Gugglesterone (FXR antagonist, 50 μM) increased above protein expressions. Meanwhile, FXR deficiency increased YAP1 activity and fibrogenesis in PS-NPs-induced BEAS-2B. Collectively, MPs/NPs exposure elevates the risk of pulmonary fibrosis, and FXR-YAP1 axis dysregulation may underlie their toxicity mechanisms. Among the tested polymers, PS exhibits stronger pulmonary toxicity and cytotoxicity compared to PE or PP, and NPs of the same polymer demonstrate greater pulmonary toxicity than MPs.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"519 ","pages":"Article 154304"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145269715","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":"Polycyclic aromatic hydrocarbons-enriched diesel exhaust particles induced hypertrophy in rat primary neonatal cardiomyocytes and apoptotic cell death in H9c2 cardiomyocytes","authors":"Ching-Chia Wang ,&nbsp;Huei-Ping Tzeng ,&nbsp;Mei-Chi Hsieh ,&nbsp;Kuo-Cheng Lan ,&nbsp;Shing-Hwa Liu","doi":"10.1016/j.tox.2025.154305","DOIUrl":"10.1016/j.tox.2025.154305","url":null,"abstract":"<div><div>There is limited research about the direct effects of diesel exhaust particles (DEPs) on cardiomyocytes. The respirable DEPs asorbed many organic substances such as polycyclic aromatic hydrocarbons (PAHs). Here, we used the standard DEPs, enriched in PAHs and their derivatives, from the National Institute of Standards and Technology of the United States and extracted the organic compounds of DEPs (DEPEs) to examine the effects and mechanisms of DEPEs on rat primary neonatal cardiomyocytes (NRCMs) and rat embryonic H9c2 cardiomyocytes. No cytotoxicity was found at DEPEs concentrations up to 25 μg/mL in NRCMs. By evidence of immunofluorescence of desmin, cellular protein content, and mRNA levels of brain natriuretic peptide and β-myosin heavy chain, the cell hypertrophy was induced by DEPEs in NRCMs. DEPEs induced cytotoxicity in H9c2 cells at the concentration of 15 μg/mL and up. DEPEs exposure significantly induced apoptosis and protein expression of phosphorylated JNK and endoplasmic reticulum stress markers glucose-regulated protein 78 and C/EBP-homologous protein in H9c2 cells. Altogether, the direct effects of PAHs-enriched DEPEs include cytotoxic effects observed in H9c2 cells at higher concentrations and hypertrophic effects in NRCMs at concentrations without cytotoxicity. These results provide the better understanding of direct effects of DEPs on cardiomyocytes.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"519 ","pages":"Article 154305"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145269717","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":"Long-term low-dose N, N-dimethylformamide exposure disturbs hepatic lipid and glucose homeostasis in mice","authors":"Shu-Jun Hong ,&nbsp;Ming-Bao Zhang ,&nbsp;Le-Yi Qi ,&nbsp;Tian-Hao Zhao ,&nbsp;Pin Wang ,&nbsp;Tao Zeng","doi":"10.1016/j.tox.2025.154329","DOIUrl":"10.1016/j.tox.2025.154329","url":null,"abstract":"<div><div><em>N, N</em>-dimethylformamide (DMF) is a widely used industrial solvent with well-documented hepatotoxicity at high exposure levels. However, some epidemiological studies suggest that occupational exposure below the current occupational exposure limits (OELs) may still have adverse effects on workers. This study was designed to investigate the hepatotoxicity of subacute (28 days) and chronic (6 months) DMF exposure at OEL-relevant levels in mice. Mice exposed to 75 mg/kg bw DMF (a dose equivalent to the OEL of 20 mg/m³) for 28 days showed no signs of liver injury, while higher doses (150 and 300 mg/kg bw) led to increased serum aminotransferase activities, elevated liver weight/body weight ratio, and reduced hepatic lipid levels. However, 6 months of DMF exposure at 75 mg/kg bw caused a significant reduction in liver lipid content, activation of AMPK, and suppression of SREBP-1c, which were accompanied by elevated fasting blood glucose (FBG) levels, increased area under the curve (AUC) in glucose tolerance tests (GTTs), and enhanced lipolysis in white adipose tissue. Increased liver weight/body weight ratio, upregulation of AMPK and p-AMPK protein expression, white adipose tissue lipolysis, elevated FBG level, and increased AUC in GTTs were also observed in mice exposed to 37.5 mg/kg bw DMF. These results indicate that chronic DMF exposure at current OELs may disrupt hepatic metabolic homeostasis, highlighting the necessity to reestablish the OELs for DMF. Further validation of these results using an inhalation exposure model in both male and female mice, with dosimetry accurately bridging to human occupational exposure, is warranted.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"519 ","pages":"Article 154329"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145422822","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":"Antiparasitic agent emodepside exerts cytotoxicity in human corneal stromal cells by blocking the interaction between mini-chromosome maintenance 6 protein (MCM6) and chromatin licensing and DNA replication factor 1 (CDT1)","authors":"Han Gao ,&nbsp;Hanyu Gao ,&nbsp;Hao Yin","doi":"10.1016/j.tox.2025.154334","DOIUrl":"10.1016/j.tox.2025.154334","url":null,"abstract":"<div><div>Emodepside, a novel antiparasitic agent, exhibits remarkable efficacy against nematodes. Recent research from a phase 2b clinical trial has demonstrated that the most frequent adverse event in the emodepside treatment group is blurred vision, but the mechanism of blurred vision remains largely unexplored. To provide references for secure medication and prospective therapeutic interventions of emodepside, we conducted an investigation into the cytotoxic effects of emodepside on the corneal stroma and its underlying mechanisms using an in vitro model of human corneal stromal (HCS) cells. The loading of the mini-chromosome maintenance 6 protein (MCM6) onto chromatin at replication origins by chromatin licensing and DNA replication factor 1 (CDT1) constitutes a crucial step in licensing DNA for replication. This study demonstrates that emodepside directly binds to the CDT1-binding domain (CBD) of MCM6, competitively blocking the MCM6-CDT1 interaction as confirmed by modified enzyme-linked immunosorbent assay and drug affinity responsive target stability assays. Molecular docking reveals that emodepside binds to CBD through hydrogen bonds with Lys754, Ile760, and Lys770. In HCS cells, this blockade results in the inhibition of DNA replication licensing and a decrease in DNA synthesis, as evidenced by the ethynyl-deoxyuridine incorporation assay, leading to cell cycle arrest at the G₀/G₁ phase. Moreover, emodepside-induced cell cycle arrest in HCS cells leads to dose-dependent apoptosis and proliferation inhibition with the IC₅₀ value being 32.3 μM. In conclusion, this study not only provides new insights into the mechanism of emodepside-induced vision blur but also offers a valuable molecular tool for the research of MCM6-CDT1 interaction.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"519 ","pages":"Article 154334"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145472066","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":"Cadmium accumulation in neuronal cells leads to essential metals imbalance and zinc transporters dysregulation","authors":"Federica Bovio ,&nbsp;Melissa Ferrian ,&nbsp;Antonia Franceschi ,&nbsp;Pasquale Melchioretto ,&nbsp;Stefano Porru ,&nbsp;Matilde Forcella ,&nbsp;Paola Fusi ,&nbsp;Chiara Urani","doi":"10.1016/j.tox.2025.154319","DOIUrl":"10.1016/j.tox.2025.154319","url":null,"abstract":"<div><div>The heavy metal cadmium (Cd), a natural element of the Earth's crust released into the environment through both natural processes and anthropogenic activities, is ranked 7th on the ATSDR Substance Priority List of hazardous substances. Its low excretion rate from human body and its long biological half-life (10–30 years) lead to Cd heavy accumulation in organisms. Although Cd carcinogenicity is well recognized, the neurotoxicity and damage to the nervous system still require further investigation. The interference with essential element homeostasis, referred as dyshomeostasis, is one of Cd neurotoxic mechanisms and its interference on specific ions balance could play a key role in the process of neurodegenerative diseases. In this study Cd possible impact on the balance of essential elements was evaluated in human neural SH-SY5Y cells, by exposing the target cells to low Cd concentrations (0.1–5 µM) for 24 h, 48 h and 6 days. Cd accumulates inside the cells in a time and dose dependent manner with dysregulation of both zinc and iron homeostasis and induction of heme oxygenase 1 expression. Moreover, zinc transporters ZnT1 and ZnT2 are upregulated, while the iron transporter DMT1 is downregulated. In conclusion our data show that even low, sublethal cadmium concentrations are effective in inducing dyshomeostasis of essential metals involved in important neuronal functions.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"519 ","pages":"Article 154319"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370499","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 potential of substances in spray-formulated degreasers and lubricants – With a literature review on asthma potentials of ammonia, maleic anhydride and methyl methacrylate","authors":"Jorid B. Sørli ,&nbsp;Hyun Kil Shin ,&nbsp;Karen B. Frydendall ,&nbsp;Eva B. Wedebye ,&nbsp;Nikolai Nikolov ,&nbsp;Marie Frederiksen ,&nbsp;Niels Hadrup","doi":"10.1016/j.tox.2025.154312","DOIUrl":"10.1016/j.tox.2025.154312","url":null,"abstract":"<div><div>Spray-formulated engine/brake cleaners and lubricants form aerosols that can deposit in the airways where toxicity can occur. Characterisation of the ingredients’ toxicity can help minimise the human risk. We recently published a database of 376 ingredient substances in 82 spray-formulated engine/brake cleaners and lubricants available in the European Union (EU) and screened them for genotoxic and carcinogenic potentials. In the current work we expand this screening to include pulmonary toxicity, neurotoxicity, hepatotoxicity and reproductive and developmental toxicity. For this we used EU harmonised classification, quantitative structure activity relationship (QSAR) models and lists of suspected asthmagens. For asthmagens we reviewed the literature. Fifteen substances had an asthma induction potential, five of which had literature to support the potential, namely: aluminium powder, ammonia, chlorine, maleic anhydride and methyl methacrylate. Other potential asthma inducers were: 1,3,5-trimethylbenzene, 1,2,4-trimethylbenzene, benzyl alcohol, methyl-2-hydroxybenzoate, 1,4-dihydroxybenzene, 2-aminoethanol, 2-aminopropanol, 1,2-benzisothiazol-3(2 H)-on, hexyl dihydrogen phosphate and diethanolamine. The number of substances with potential for the other toxicities are: acute toxicity when inhaled (8 substances), aspiration toxicity (13), neurotoxicity (13), reproductive/developmental toxicity (34) and hepatotoxicity (76). The fractions of products containing substances with potential for the toxicities were: asthma (18 % of the products), acute toxicity when inhaled (12 %), neurotoxicity (55 %), reproductive/developmental toxicity (63 %) and hepatotoxicity (52 %). Finally, we discuss substances to be prioritised as of highest concern. In conclusion, we identified a substantial toxic potential with the employed screening methods. The data can be used in safe-by-design substitution of potentially toxic substances and inform hazard assessment of spray-formulated engine/brake cleaners and lubricants.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"519 ","pages":"Article 154312"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313817","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":"Adolescent exposure to polylactic acid microplastics causes cardiac fibrosis by promoting cardiomyocyte senescence","authors":"Chun Pan ,&nbsp;Shoujun Li ,&nbsp;Tingting Liu ,&nbsp;Yujie Shi ,&nbsp;Zongheng Cai ,&nbsp;Xinyu Luo ,&nbsp;Silong Xia","doi":"10.1016/j.tox.2025.154318","DOIUrl":"10.1016/j.tox.2025.154318","url":null,"abstract":"<div><div>Population studies and animal experiments have indicated that exposure to microplastics (MPs) is closely related to adverse cardiovascular outcomes. However, as far as we know, all current studies on MPs-induced cardiotoxicity are limited to traditional petroleum-based plastics, and there is a blank for potential heart damage caused by 'bioplastics' made of polylactic acid (PLA) materials. This study investigated the cardiotoxicity of PLA-MPs in mice and its potential mechanism. Adolescent mice exposed to PLA-MPs for 28 days showed obvious cardiac developmental toxicity, manifested as disordered arrangement of myocardial cells, thinning of myocardial thickness and fibrosis. Further studies found that ferroptosis and senescence were observed in the hearts of adolescent mice exposed to PLA-MPs. <em>In vitro</em>, we used H9c2 cells to study the cellular internalization, senescence and ferroptosis effects of PLA-MPs. We found that PLA-MPs exposure increased the senescence characteristics of H9c2 cells, such as increased SA-β-Gal activity, up-regulated expression of senescence-associated proteins (p16, p21, γH2AX) and senescence-associated inflammatory factors. Moreover, we found that PLA-MPs caused ferroptosis in H9c2 cells with elevated ferrous iron. Subsequent studies found that Fer-1 inhibited ferroptosis signal and alleviated PLA-MPs-induced H9c2 cell senescence. In summary, our findings highlight the cardiotoxic effects of biodegradable PLA-MPs through ferroptosis and senescence pathways, and provide insights into the toxicological effects of biodegradable MPs on mammalian cardiovascular system capacity.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"519 ","pages":"Article 154318"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145347507","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 dysbiosis of gut microbiota attributes to the impairment of blood-brain barrier in rats triggered by cadmium","authors":"Tao Wang ,&nbsp;Xinyu Huang ,&nbsp;Le Lu ,&nbsp;Xianzu Luo ,&nbsp;Yi Wang ,&nbsp;Yonggang Ma ,&nbsp;Xishuai Tong ,&nbsp;Hui Zou ,&nbsp;Jianhong Gu ,&nbsp;Xuezhong Liu ,&nbsp;Jianchun Bian ,&nbsp;Zongping Liu ,&nbsp;Yan Yuan","doi":"10.1016/j.tox.2025.154303","DOIUrl":"10.1016/j.tox.2025.154303","url":null,"abstract":"<div><div>Cadmium (Cd) is a non-biodegradable heavy metal with a long biological half-life that is detrimental to human health. As Cd can increase blood-brain barrier (BBB) permeability and disturb the gut microbiota, the relationship between the BBB and gut microbiota disturbance induced by Cd consumption remains unclear. This study aims to identify whether Cd-induced gut microbiota dysbiosis is associated with rat BBB injury and investigate the possible mechanism. Here, we conducted analyses of variations in the composition of the gut microbiota and its metabolites, as well as BBB permeability and the results of the Morris water maze test, in rats treated with Cd by gavage. Fecal microbiota transplantation was performed to verify the role of the microbiota in altering BBB permeability induced by Cd. The results showed that Cd disturbed the gut microbiota, decreasing the levels of short-chain fatty acids (SCFAs). Furthermore, Cd-induced BBB permeability was substantiated by FITC-dextran leakage, ultrastructural observations, and diminished Claudin-5, Occludin, and ZO-1 protein expression, all of which were mitigated by FMT. In vitro, sodium butyrate (SOB) alleviated Cd-induced oxidative stress and increased the expression levels of GPX4 and FTH. Taken together, these findings suggest that Cd disrupts the microbiota and SCFAs components in rats, thereby contributing to BBB damage. SOB prevents Cd-induced BBB damage by suppressing ferroptosis in microvascular endothelial cells. This exhaustive study considerably enhances our comprehension of the health hazards posed by Cd to the central nervous system via the gut-brain axis.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"519 ","pages":"Article 154303"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275901","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":"Investigation of hepatotoxicity of acrylamide using mass spectrometry-based proteomics and N-glycoproteomics in mouse model","authors":"Menghui Xiang,&nbsp;Zhixin Tian","doi":"10.1016/j.tox.2025.154316","DOIUrl":"10.1016/j.tox.2025.154316","url":null,"abstract":"<div><div>Acrylamide is a widely used and distributed chemical proven to be a hepatotoxicant; however, the toxicological mechanisms on post-translational modifications regulation, which is most relevant to regulating the activity of proteins, are largely unknown. Here we report mass spectrometry-based toxico-proteomics and N-glycoproteomics study of AA using ICR mouse model with the exposure experimental group and the wild-type control group. 16,640 peptides from 2,956 proteins and 19,613 intact N-glycopeptides from 3,515 N-glycoproteins were identified in proteomics and N-glycoproteomics, where 99 differentially expressed proteins and 303 differentially expressed intact N-glycopeptides from 150 N-glycoproteins were quantified. Functional annotation of differentially expressed proteins and N-glycoproteins enables identification of AA hepatotoxicity pathways of autophagy, apoptosis and inflammation through stresses of reactive oxygen species and endoplasmic reticulum. 11 potential N-glycoprotein biomarkers were filtered through interactome and functional network analysis, and 5 (UGT1A9, CTSD, PSAP, CES1F and CD163) of them with more than 50 % frequency occurrence in parallel reaction monitoring verification experiment. These results provide a deep and comprehensive understanding of AA hepatotoxicity, especially from the perspective of N-glycoproteins; in addition, the integrated proteomics and N-glycoproteomics pipeline can be extended to the study of other toxicants.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"519 ","pages":"Article 154316"},"PeriodicalIF":4.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329882","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}