Toxicology最新文献

{"title":"Assessment of toxicity associated with inhalation of potentially toxic elements present in combustible tobacco products: cigars, pipe tobacco, bidis and cigarettes – An evaluation of risk assessment issues","authors":"Paweł Hać ,&nbsp;Satoki Okabayashi ,&nbsp;Motohiro Tsuboi ,&nbsp;Bartłomiej Michał Cieślik ,&nbsp;Piotr Konieczka","doi":"10.1016/j.tox.2025.154092","DOIUrl":"10.1016/j.tox.2025.154092","url":null,"abstract":"<div><div>Smoking-related diseases represent a substantial global health challenge, particularly given the direct inhalation of smoke into the vulnerable respiratory system. This method of consumption presents a challenge in classifying smoking in terms of exposure to toxins, in comparison to other forms of environmental contamination, such as food or air pollution. Combustible tobacco products (CTPs), including cigars, pipe tobaccos, bidis, and cigarettes, are therefore among the most toxic materials with a wide range of adverse health effects. The majority of studies on toxic elements in CTPs concentrate on cigarettes, with other forms of tobacco receiving comparatively little attention. Furthermore, there is currently no established methodology for estimating consumer exposure to these elements regarding smoke inhalation. The aim of this study was to estimate the exposure of consumers to potentially toxic elements (PTEs) in various CTPs, utilising a model adapted from food chemistry but considering air pollution exposure levels and the distinctive characteristics of smoking. The findings indicate that the inhalation of smoke from less than 0.5 g of tobacco can deliver hazardous doses of elements, such as Ni (noncancer risk) or As (carcinogenic risk). This suggests that inhalation of toxic elements in cigarette smoke significantly contributes to tobacco-related health risks.</div></div><div><h3>Statement of Environmental Implication</h3><div><ul><li><span>1.</span><span><div>The analyzed tobacco and the determined potentially toxic elements themselves are contaminating materials and compounds as they have hazardous effects on the environment and humans.</div></span></li></ul><ul><li><span>2.</span><span><div>The results of the study represent environmentally relevant conditions, as the analysis was made on real tobacco product samples and the calculations were appropriately modelled to estimate actual human exposure conditions.</div></span></li></ul></div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"514 ","pages":"Article 154092"},"PeriodicalIF":4.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587138","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":"NAM-based analysis of contaminant short-term organ toxicity in HepaRG and RPTEC/TERT1 cells","authors":"Kristina Jochum ,&nbsp;Andrea Miccoli ,&nbsp;Cornelia Sommersdorf ,&nbsp;Oliver Poetz ,&nbsp;Albert Braeuning ,&nbsp;Tewes Tralau ,&nbsp;Philip Marx-Stoelting","doi":"10.1016/j.tox.2025.154104","DOIUrl":"10.1016/j.tox.2025.154104","url":null,"abstract":"<div><div>New Approach Methodologies (NAMs), including cell culture and multi-level omics analyses, are promising alternatives to animal testing. To become useable for risk assessment purposes, they have to be applicable for different substance groups. One important group of substances is food contaminants, including synthetic chemicals, such as perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), and natural compounds, such as mycotoxins and pyrrolizidine alkaloids. We tested five known contaminants affecting the liver and/or the kidney – PFOS, PFOA, Aflatoxin B₁ (AB₁), lasiocarpine (Las), and cadmium chloride – using HepaRG and RPTEC/TERT1 cells at non-cytotoxic concentrations for 36 and 72 h. Our NAM-based testing protocol included marker protein analysis for cellular functions and targeted transcriptomics followed by bioinformatics pathway analysis. The effects observed were compared with established <em>in vivo</em> results. Protein analysis indicated various affected pathways in HepaRG cells, with generally fewer effects in RPTEC/TERT1 cells. The strongest transcriptional impact was noted for Las in HepaRG cells. This study demonstrated the test protocol's applicability across different substances, revealing significant differences between HepaRG and RPTEC/TERT1 cell lines. RPTEC/TERT1 cells, while expressing renal-specific CYP enzymes, were less suitable for detecting effects of substances requiring hepatic metabolic activation, like Las and AB₁. Our data supports the concept of specific pathway toxicity, with pathway analysis enabling the prediction of effects based on mechanism rather than target organ. Employing multiple omics techniques provided comprehensive insights into various compound effects, including steatosis, reactive oxygen species production and DNA damage, highlighting the potential of an extended omics approach for advancing toxicological assessments.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"514 ","pages":"Article 154104"},"PeriodicalIF":4.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587140","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":"H3K18 lactylation-mediated SIX1 upregulation contributes to silica-induced epithelial-mesenchymal transition in airway epithelial cells","authors":"Songtao Liu ,&nbsp;Yiting He ,&nbsp;Linling Jin ,&nbsp;Shuangshuang Shi ,&nbsp;Jiayi Zhang ,&nbsp;Weiping Xie ,&nbsp;Mingxia Yang ,&nbsp;Qun Zhang ,&nbsp;Hui Kong","doi":"10.1016/j.tox.2025.154109","DOIUrl":"10.1016/j.tox.2025.154109","url":null,"abstract":"<div><div>Silica exposure-induced airway epithelial-mesenchymal transition (EMT) is a critical pathological process in pulmonary fibrosis. This study investigated the role of NLRP3 inflammasome, glycolysis, and histone lactylation in silica-induced EMT of human bronchial epithelial cells (16HBE). Silica exposure activated NLRP3 inflammasome, enhanced glycolysis and H3K18 lactylation, as well as induced EMT in 16HBE cells. Selective inhibition of NLRP3 inflammasome with MCC950, blockade of the interleukin 1 (IL-1) receptor with AF12198, or suppression of lactate production with oxamate effectively reduced glycolysis-mediated histone lactylation and mitigated silica-induced EMT. Moreover, silica-induced upregulation of PFKFB3, a key enzyme of glycolysis, was significantly mitigated by MCC950 or AF12198. Cut&amp;Tag analysis revealed silica treatment led to H3K18 lactylation enrichment at transcription start sites (TSS), particularly within the promoter region of the sine oculis homeobox 1 (SIX1), which enhanced transcription of SIX1, a key transcription factor involved in EMT. Consistently, inhibition of histone lactylation by the histone acetyltransferase P300 inhibitor A-485 suppressed silica-induced SIX1 expression and EMT. These findings indicate that silica activates NLRP3 inflammasome and promotes interleukin 1β (IL-1β) production, thereafter enhancing PFKFB3-mediated glycolysis by IL-1 receptor. Lactate accumulation by glycolysis enhances H3K18 lactylation at the TSS facilitating expression of SIX1. Together, this inflammation-glycolysis-lactylation cascade involved in EMT provides new insights into the molecular mechanisms underlying silica-induced pulmonary fibrosis.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"514 ","pages":"Article 154109"},"PeriodicalIF":4.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574064","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":"Enhancing DILI toxicity prediction through integrated graph attention (GATNN) and dense neural networks (DNN)","authors":"Agung Surya Wibowo ,&nbsp;Kil To Chong ,&nbsp;Hilal Tayara","doi":"10.1016/j.tox.2025.154108","DOIUrl":"10.1016/j.tox.2025.154108","url":null,"abstract":"<div><div>Drug-induced liver injury (DILI) toxicity is a condition when drugs have a destructive effect on the liver organ. The prediction of this toxicity becomes crucial in the drug development process to guarantee that drugs are safe from toxicity. Assessment is usually carried out in the conventional laboratory, which causes a high cost in materials and time. To help solve the problem, computational technology is used to predict DILI toxicity in compounds and drugs. Many researchers have developed the model by using various molecular datasets. The Simplified molecular input line entry system (SMILES) code data was used to represent drugs or compounds. In this work, we proposed the modified model using the reliable dataset from the previous work. We reproduced the best previous model and combined it with the graph attention neural network. After running the proposed model, the performances outperformed almost all performance metrics of the previous model by 75.14 % precision, 85.2 % sensitivity, 39.9 % MCC value, 75.7 % AUC value and 82.5 % F1 score. All the source code used in the experiment can be accessed freely at this link: <span><span>https://github.com/asw1982/GATNN</span><svg><path></path></svg></span> DNN DILI Toxicity.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"514 ","pages":"Article 154108"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543663","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":"Meg3-NONO-RAR axis mediates RA pathway activation in TCDD-induced cleft palate","authors":"Zengli Yu ,&nbsp;Hexin Su ,&nbsp;Zhan Gao ,&nbsp;Yao Chen ,&nbsp;Yuwei Zhang ,&nbsp;Wenjing Duan ,&nbsp;Tingting Zhang ,&nbsp;Xiangdong Wang ,&nbsp;Dongliang Xu ,&nbsp;Xiaozhuan Liu","doi":"10.1016/j.tox.2025.154099","DOIUrl":"10.1016/j.tox.2025.154099","url":null,"abstract":"<div><div>Dioxins, a group of environmental pollutants, can cause developmental toxicity through interaction with the aromatic hydrocarbon receptor (AHR). Retinoic acid (RA) functions via binding to retinoic acid receptor (RAR)/retinoid X receptor (RXR). Both AHR and RA pathways can be activated by dioxins. TCDD or atRA exposure similarly alters the expression of the long non-coding RNA (lncRNA) Meg3 in mouse palatal tissue. This study further examined the mechanism of TCDD-induced cleft palate (CP) via the RA pathway in mouse embryonic palatal mesenchymal (MEPM) cells. Results showed that in MEPM cells TCDD treatment increased Meg3 and RARA expression, inhibited cell proliferation, and had a synergistic effect with atRA. RNA pull-down-MS and RIP assays revealed that Meg3 binds to NONO, which belongs to the drosophila behavior human splicing family (DBHS) and have been reported to be associated with cell cycle regulation. NONO interacts with RAR and inhibits RARA expression. TCDD and atRA treatment reduced NONO expression. Silencing Meg3 raised NONO levels and mitigated the impact of TCDD or atRA on RA pathway activation, cell proliferation and survival. These findings suggest that TCDD affects Meg3 and NONO expression and the RA pathway activation, Meg3 interacts with NONO which may regulate RARA in palatal tissue. Thus, we propose that the RA pathway activation in TCDD-induced cleft palate may be mediated by the Meg3-NONO-RAR axis.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"514 ","pages":"Article 154099"},"PeriodicalIF":4.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537581","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":"Using new approach methodologies for the identification of a sensitizing co-formulant in a plant protection product","authors":"Stefanie Seifert ,&nbsp;Katherina Siewert ,&nbsp;Caterina Curato ,&nbsp;Anna Sonnenburg ,&nbsp;Nele Fritsch ,&nbsp;Matthias Peiser ,&nbsp;Christian Tobias Willenbockel ,&nbsp;Sabine Martin ,&nbsp;Denise Bloch","doi":"10.1016/j.tox.2025.154100","DOIUrl":"10.1016/j.tox.2025.154100","url":null,"abstract":"<div><div>According to Regulation (EC) No 1272/2008, plant protection products (PPPs) can be classified for skin sensitisation by either considering the full formulation or the individual components. For a fraction of PPPs, an application of both assessment strategies results in discrepant classification results. We here aimed to resolve this discrepancy for PPP 1, an exemplary product, which was classified as sensitizing by a positive local lymph node assay but scored negative by the component-based method. We collected further data, as suggested by the regulation, based on a combination of new approach methodologies (NAMs) covering several key events (KEs) in the adverse outcome pathway model for skin sensitisation. Precisely, we employed quantitative structure activity relationship (QSAR) analysis (KE 1), the human cell line activation test (h-CLAT) complemented by Interleukin-8 release measurements (KE 3) and a novel short-term T cell test that is based on the induced expression of activation markers (KE 4). We tested the complete product, individual co-formulants (CFs) or single substances. PPP 1 tested positive in all <em>in vitro</em> assays. QSAR analysis revealed two CFs containing sensitizing chemicals. Only CF 1 was tested positive in the h-CLAT at a minimal induction threshold of 1.5 mg/mL, being less potent than PPP 1. In the T cell assay, both PPP 1 and CF 1 were tested positive at around 0.1 mg/mL. In conclusion, our results propose a novel integrated NAM-based strategy that should be explored further for skin sensitisation hazard identification of complex mixtures, such as PPPs.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"514 ","pages":"Article 154100"},"PeriodicalIF":4.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537591","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":"Sintilimab combined with acetaminophen aggravates liver injury through apoptotic and disturbed bile acid pathways","authors":"Jianing Qin ,&nbsp;Bin Yu ,&nbsp;Yuanyuan Zhou ,&nbsp;Wenqiang Huang ,&nbsp;Zhanxiong Luo ,&nbsp;Rixin Chen ,&nbsp;Haizhou Liu ,&nbsp;Fang Wu","doi":"10.1016/j.tox.2025.154106","DOIUrl":"10.1016/j.tox.2025.154106","url":null,"abstract":"<div><div>Sintilimab, an immune checkpoint inhibitor, and acetaminophen (APAP), a common analgesic, have been implicated in hepatotoxicity. However, their combined effect on liver injury remains understudied. This study investigated the exacerbating hepatotoxic effects of sintilimab in combination with APAP in mice, focusing on the apoptotic markers and bile acids disruptions. We found that their combination significantly increased serum liver enzymes (aminotransferase and alanine aminotransferase), induced histological liver damage, and boosted hepatic oxidative stress markers (reactive oxygen species, 8-hydroxy-2’-deoxyguanosine, malondialdehyde) while depleting glutathione. Furthermore, the co-treatment also heightened apoptotic markers (cytochrome C, caspase-9, caspase-3, Bax) compared to the control and APAP group alone, indicating a more pronounced apoptotic response. Additionally, it downregulated CYP7A1 expression and disrupted bile acid metabolism, characterized by decreased levels of primary bile acids and increased levels of secondary bile acids, suggesting a role in the aggravated liver injury. This highlights the potential mechanism by which sintilimab and APAP interact, leading to increased oxidative stress, apoptosis and disruption of bile acid homeostasis, which together contribute to the exacerbation of liver injury. The study underscores the need for caution when co-administering sintilimab and APAP, emphasizing the importance of monitoring liver injury to mitigate the risk of combined drug use.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"514 ","pages":"Article 154106"},"PeriodicalIF":4.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537587","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":"Effects of methoxychlor on broiler gut microbiota and liver and its residue accumulation risk to human health","authors":"Yutong Tang,&nbsp;Ying Liu,&nbsp;Yongpeng Jin,&nbsp;Wanjun Zhang,&nbsp;Gaoyi Liu,&nbsp;Yiqiang Chen","doi":"10.1016/j.tox.2025.154105","DOIUrl":"10.1016/j.tox.2025.154105","url":null,"abstract":"<div><div>Methoxychlor as a persistent organic pollutant poses significant risks to human health and the environment. Most toxicological studies focus on high-dose exposures, which do not reflect typical chronic and low-dose human exposure, necessitating the examination of the cumulative effects of chronic exposure to persistent organic pollutants. Our study exposed broilers to different concentrations of p,p’-methoxychlor (0.01–5 mg/kg) in feed, reflecting the doses commonly used in agricultural practices. The results show that even at low doses, methoxychlor causes liver damage, metabolic disturbances, disrupts the intestinal microbiota, and leads to significant accumulation of residues, particularly in the liver. When methoxychlor contamination in the feed exceeds 0.01 mg/kg, residue levels in the broiler liver surpass the EU-established limit, and the residue levels in the broiler muscle surpass this limit when contamination exceeds 0.2 mg/kg. In addition, methoxychlor disrupts the gut microbiota, causing significant shifts in microbial composition, including a decrease in beneficial bacteria and an increase in potentially harmful taxa. The gut dysbiosis, bioaccumulation potential of methoxychlor and changes in liver metabolic indicators may be associated with the liver pathology observed in this study, warranting further investigation. The harmful consequences significantly impact broiler production, leading to food safety concerns and risks to human health. At similar exposure levels, humans may face health risks comparable to those observed in broilers. This study provides important evidence for establishing strict regulations on methoxychlor residues in food products and assessing the potential risks of low-dose and long-term exposure to methoxychlor.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"514 ","pages":"Article 154105"},"PeriodicalIF":4.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531818","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":"Molecular mechanism of programmed cell death in drug-induced neuronal damage: A special focus on ketamine-induced neurotoxicity","authors":"Peipei Wang ,&nbsp;Tong Niu ,&nbsp;Degao Huang,&nbsp;Yuanlong Li,&nbsp;Zihan Jiang,&nbsp;Xia Wang,&nbsp;Linchuan Liao","doi":"10.1016/j.tox.2025.154102","DOIUrl":"10.1016/j.tox.2025.154102","url":null,"abstract":"<div><div>In recent years, the abuse of ketamine as a recreational drug has been growing, and has become one of the most widely abused drugs. Continuous using ketamine poses a risk of drug addiction and complications such as attention deficit disorder, memory loss and cognitive decline. Ketamine-induced neurotoxicity is thought to play a key role in the development of these neurological complications. In this paper, we focus on the molecular mechanisms of ketamine-induced neurotoxicity. According to our analyses, drugs in causing neurotoxicity are closely associated with programmed cell death (PCD) such as apoptosis, autophagy, necroptosis, pyroptosis, and Ferroptosis. Therefore, this review will collate the existing mechanisms of programmed death in ketamine-induced neurotoxicity as well as explore the possible mechanisms by outlining the mechanisms of programmed death in other drug-induced neurotoxicity, which may be helpful in identifying potential therapeutic targets for neurotoxicity induced by ketamine abuse.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"513 ","pages":"Article 154102"},"PeriodicalIF":4.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511627","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":"Synergistic effects of lead and copper co-exposure on promoting oxidative stress and apoptosis in the neuronal cells","authors":"Di Wu ,&nbsp;Desheng Wang ,&nbsp;Shuang-Shuang Tan ,&nbsp;Yu-Qi Li ,&nbsp;Su-Li Hong ,&nbsp;Tao Wang ,&nbsp;Gang Zheng","doi":"10.1016/j.tox.2025.154103","DOIUrl":"10.1016/j.tox.2025.154103","url":null,"abstract":"<div><div>Exposure to lead (Pb) or copper (Cu) is common and has been associated with increased risk of neurodegenerative disease. However, combined neurotoxic effects of co-exposure to these elements remain unclear. This study aimed to determine the toxic effects of Pb and Cu co-exposure on HT22 cells. In this study, Pb and Cu co-exposure exhibited enhanced toxicity, including increased reactive oxygen species (ROS) and Malondialdehyde (MDA) levels, Superoxide Dismutase 1 (SOD1) activity, lower cell viability and higher apoptotic rates, compared to single-element exposure. Pb and Cu co-exposure also resulted in significantly increased cellular labile Cu level by altering the protein levels of Cu transporters, including Copper Transporter-1 (CTR1), ATPase Copper Transporting-α(ATP7A) and ATPase Copper Transporting-β (ATP7B). Treating with antioxidants or Cu chelator to the co-exposed cells blocked the reduction cell viability and elevation of apoptotic rates. This study suggests that Pb and Cu co-exposure can result in a synergistic toxicity in neuronal cells by inducing oxidative stress and apoptosis. The cellular Cu accumulation may play an important role in inducing these synergistic effects, and both antioxidation and Cu chelation may be promising control measures to alleviate the neurotoxicity of Pb and Cu co-exposure.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"513 ","pages":"Article 154103"},"PeriodicalIF":4.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511163","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}