Toxicology最新文献

{"title":"Mechanisms involved in pro-inflammatory responses to traffic-derived particulate matter (PM) in THP-1 macrophages compared to HBEC3-KT bronchial epithelial cells","authors":"Marit Låg ,&nbsp;Tonje Skuland ,&nbsp;Jarle Ballangby ,&nbsp;Vegard Sæter Grytting ,&nbsp;Rikke Bramming Jørgensen ,&nbsp;Brynhild Snilsberg ,&nbsp;Johan Øvrevik ,&nbsp;Jørn A. Holme ,&nbsp;Magne Refsnes","doi":"10.1016/j.tox.2025.154174","DOIUrl":"10.1016/j.tox.2025.154174","url":null,"abstract":"<div><div>The pro-inflammatory responses in THP-1-derived macrophages and human bronchial epithelial cells (HBEC3-KT) were examined after exposure to size-fractioned particulate matter (PM) sampled in two road tunnels. All tunnel PM samples induced release and expression of CXCL8 and IL-1β in THP-1 macrophages (50 µg/mL) and HBEC3-KT cells (100 µg/mL), but the potency of the samples differed between the cell types. The road tunnel PM induced pro-inflammatory responses in the macrophages to a much higher extent than diesel exhaust particles (DEP) and particles derived from the stone materials used in the asphalt. Tunnel PM induced a markedly higher increase in cytochrome P450 (CYP)1A1 expression in HBEC3-KT cells than in THP-1 macrophages. The content of organic carbon (OC) in PM correlated to the release of CXCL8 in HBEC3-KT cells, but not in THP-1 macrophages. Moreover, the aryl hydrocarbon receptor (AhR)-inhibitor CH223191 and the antioxidant N-acetyl cysteine (NAC) reduced the PM-induced cytokine release in the macrophages to a lower extent than in HBEC3-KT. In contrast, a toll-like receptor (TLR)2 antibody markedly reduced the PM-induced responses in THP-1 macrophages, but not in HBEC3-KT. A TLR4 antibody was without effect in both cell types. The levels of the microbial TLR2-ligand β-glucan in the PM samples were in a range that might be sufficient to induce pro-inflammatory responses. However, a microbial-independent mechanism could also be involved. In support of such a mechanism, the pro-inflammatory responses to a sample of α-quartz (Min-U-Sil 5), with low levels of β-glucan, were reduced by anti-TLR2. In conclusion, our results indicate that traffic-derived PM exert pro-inflammatory responses in THP-1 macrophages and HBEC3-KT cells via different PM constituents and mechanisms. OC/AhR-dependent mechanisms appeared to be important for PM-induced CXCL8 responses in HBEC3-KT cells, while the cytokine responses in THP-1 macrophages seemed to involve TLR2-mediated activation, either via β-glucan-dependent or -independent mechanisms.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"516 ","pages":"Article 154174"},"PeriodicalIF":4.8,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143943185","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":"Environmentally relevant concentrations of individual per- and polyfluoroalkyl substances (PFAS) and a PFAS mixture impact proliferation, migration, and gene transcription in a human myometrial cell line","authors":"Kendra L. Clark ,&nbsp;Jitu W. George","doi":"10.1016/j.tox.2025.154173","DOIUrl":"10.1016/j.tox.2025.154173","url":null,"abstract":"<div><div>Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants linked to adverse health effects. Epidemiological studies have linked PFAS with an increased risk of uterine diseases including fibroids however, the mechanisms involved remain to be elucidated. This study examined the impact of individual PFAS, such as legacy compounds [perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS)] and alternative short-chain compounds [GENX/HFPO-DA and perfluorobutanesulfonic acid (PFBS)], along with a PFAS mixture, on the function and transcriptome of immortalized human myometrial cells (UT-TERT). Exposure to these PFAS resulted in increased cell viability and proliferation. Flow cytometry showed that PFOS and the PFAS mixture altered cell cycle progression, while migration assays indicated significant enhancement of cell migration following PFOS and mixture exposure. Moreover, PFOA, PFBS, and the PFAS mixture impaired gap junction intercellular communication (GJIC), suggesting possible disruptions in cellular communication in the uterine environment. Transcriptomic analysis identified extensive changes in gene expression after exposure to environmentally relevant PFAS levels, revealing common molecular pathways involved in cell signaling, lipid metabolism, and cell survival. These findings provide crucial insights into how PFAS may contribute to reproductive health risks, warranting further investigation into the long-term effects of PFAS on uterine function and overall reproductive health.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"515 ","pages":"Article 154173"},"PeriodicalIF":4.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143911712","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":"Changes of N6-methyladenosine and ferroptosis in cadmium-induced reproductive toxicity of male mice fed a high fat and high sugar diet","authors":"De Liu ,&nbsp;Yuan Zhao ,&nbsp;Jiao Dai ,&nbsp;Rongxian Li ,&nbsp;Jiamin Yuan ,&nbsp;Kaiyan Shen ,&nbsp;Zuoshun He ,&nbsp;Shiyan Gu","doi":"10.1016/j.tox.2025.154172","DOIUrl":"10.1016/j.tox.2025.154172","url":null,"abstract":"<div><div>Cadmium (Cd) and high-fat and high-sugar diet (HFHS) are risk factors contributing to the decline in male sperm quality. N⁶-methyladenosine (m⁶A) is essential in the processes of testicular development and spermatogenesis. Ferroptosis, a form of cell death that depends on iron, is prone to causing testicular dysfunction. However, the changes in m⁶A modification regulatory proteins and ferroptosis signaling molecules in male mice with sperm abnormalities resulting from combined exposure to Cd and HFHS remain incompletely elucidate. Our present data indicate that the combined treatment of Cd and HFHS significantly reduced sperm quality in comparison to those in single Cd or HFHS treatment. In addition, indicators related to ferroptosis in the combined treatment of Cd and HFHS group have also undergone significant changes. In detail, the contents of malondialdehyde (MDA) and Fe²⁺ as well as Slc7a11 expression were increased while Gclc expressions were reduced in the testicular tissue of Cd and HFHS combined treatment mice. Further detect results showed that the combined exposure to Cd and HFHS synergistically elevated the m⁶A modification levels alongside a downregulation of the Mettl3, Fto, Alkbh5 and Ythdc2 at the protein level when compared with those in single Cd or HFHS treatment. Altogether, it can be inferred that Cd and HFHS combined treatment may alter the levels of m⁶A modification regulatory proteins in testicular tissue, leading to increased Fe²⁺ and MDA production, thus activating the Slc7a11/Gpx4 signaling pathway, ultimately decreasing the sperm quality in mice, providing preliminary evidence for the occurrence of ferroptosis in testicular cells. Our findings may provide direction for the study of reproductive toxicity of cadmium and offer reference for the selection of molecular targets.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"516 ","pages":"Article 154172"},"PeriodicalIF":4.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931505","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 Alarming Consequences of Workforce Reductions at the FDA, EPA, NIH and CDC in the United States","authors":"Martin van den Berg PhD (Editor-in-Chief, Regulatory Toxicology & Pharmacology and Current Opinion in Toxicology) ,&nbsp;Daniel R. Dietrich PhD (Editor-in-Chief, Chemico-Biological Interactions, Computational Toxicology, and Journal of Toxicology and Regulatory Policy) ,&nbsp;Sonja von Aulock PhD (Editor-in-Chief, ALTEX – Alternatives to Animal Experimentation) ,&nbsp;Anna Bal-Price PhD (Editor-in-Chief, Reproductive Toxicology) ,&nbsp;Michael D. Coleman PhD (Editor-in-Chief, Environmental Toxicology and Pharmacology) ,&nbsp;Mark T.D. Cronin PhD (Editor-in-Chief, Computational Toxicology) ,&nbsp;Paul Jennings PhD (Editor-in-Chief, Toxicology in Vitro) ,&nbsp;Angela Mally PhD (Editor-in-Chief, Toxicology Letters) ,&nbsp;Mathieu Vinken PhD (Editor-in-Chief, Toxicology and NAM Journal) ,&nbsp;Matthew C. Wright PhD (Editor-in-Chief, Food and Chemical Toxicology)","doi":"10.1016/j.tox.2025.154171","DOIUrl":"10.1016/j.tox.2025.154171","url":null,"abstract":"","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"515 ","pages":"Article 154171"},"PeriodicalIF":4.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937186","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":"Immunotoxic effect and mechanisms of Fusarium mycotoxins on human immune cells: A focus on T cells and macrophages","authors":"Jing Yang ,&nbsp;Xiaohong Wang ,&nbsp;Qiannan Zhang ,&nbsp;Hongyang Cui ,&nbsp;Lijuan You ,&nbsp;Zhisen Zhuang ,&nbsp;Yaru Tian ,&nbsp;Xiaomin Han ,&nbsp;Miaoying Shi ,&nbsp;Li Bai ,&nbsp;Xudong Jia ,&nbsp;Hui Yang","doi":"10.1016/j.tox.2025.154170","DOIUrl":"10.1016/j.tox.2025.154170","url":null,"abstract":"<div><div><em>Fusarium</em> mycotoxins, including deoxynivalenol (DON), 15-acetyl-deoxynivalenol (15-Ac-DON), 3-acetyl-deoxynivalenol (3-Ac-DON), and nivalenol (NIV), are prevalent contaminants in food and animal feed, posing significant health risks to humans. Although immunotoxicity is acknowledged as a sensitive endpoint for DON exposure, the immunotoxic effects and mechanisms of its acetylated derivatives and NIV, especially in human-derived immune cells, are not fully elucidated. In this study, we explored the toxicological impacts and mechanisms of these mycotoxins on human immune cells, with a focus on T cells and macrophages. After treating human-derived cell models with four fungal toxins (0–5000 nM) for 48 h, Jurkat T cells showed heightened sensitivity to these mycotoxins, with NIV exhibiting the highest cytotoxicity, followed by DON, 15-Ac-DON, and 3-Ac-DON. Notably, these four mycotoxins dose-dependently inhibited the activation of human T cells in the Peripheral Blood Mononuclear Cells (PBMCs) model at much lower exposure levels (0–200 nM). Similarly, after treating macrophages with NIV (0–500 nM), DON (0–1000 nM), and 15-Ac-DON (0–1000 nM) for 48 h, dose-dependent inhibition of macrophage alternative activation, lysosomal biosynthesis, and cytokine production were observed. Transcriptomic analyses indicated that DON, 15-Ac-DON, and NIV disrupt ribosome biogenesis and protein processing pathways in both T cells and macrophages. These findings underscore the influence of chemical structure on the toxicity of <em>Fusarium</em> mycotoxins and provide critical insights into their immunotoxic mechanisms.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"515 ","pages":"Article 154170"},"PeriodicalIF":4.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902543","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":"Exposure to organophosphate flame retardants and phthalates alters neuronal activity and network development","authors":"Lennart V.J. van Melis,&nbsp;Kyra N. Zimnik,&nbsp;Arjuna R. Persad,&nbsp;Teije Bak,&nbsp;Manon J.H. van Rossum,&nbsp;Regina G.D.M. van Kleef,&nbsp;J. Pepijn Wopken,&nbsp;Juliette Legler,&nbsp;Remco H.S. Westerink","doi":"10.1016/j.tox.2025.154168","DOIUrl":"10.1016/j.tox.2025.154168","url":null,"abstract":"<div><div>Exposure to organophosphate flame retardants (OPFRs) and phthalates is associated with neurodevelopmental deficits, impaired neuronal proliferation and differentiation, altered neurotransmitter levels, and impaired learning and memory. Here, we assessed the effects of acute and chronic exposure to the OPFR triphenyl phosphate (TPhP) and several phthalates on neuronal activity and network development in male and female rat primary cortical cultures grown on micro-electrode arrays. Acute exposure to TPhP, diethyl phthalate (DEP), dibutyl phthalate (DBP), and benzyl butyl phthalate (BBzP) inhibited neuronal activity, while chronic exposure to TPhP and DEP induced a hyperexcitation. Chronic exposure to DBP, BBzP, bis(2-ethylhexyl) phthalate (DEHP), and its metabolite mono-2-ethylhexyl phthalate (MEHP) inhibited neuronal network development. Exposure to BBzP and DEHP affected neuronal function at human-relevant concentrations as low as 1 µM. Acute and chronic exposure to the metabolites of DEP, DBP, and BBzP had only limited effects. Although the underlying mechanisms remain to be elucidated, analysis of endocrine mechanisms, including retinoic acid, retinoic X, liver X, and prostaglandin E₂ receptor, suggested that the effects of OPFR and phthalates were not endocrine-mediated. Further research is needed to elucidate the mechanisms underlying the different responses to acute and chronic exposure. Taken together, these results add to the evidence that TPhP and various phthalates illicit neurotoxic effects, some at low concentrations. These novel results should be considered in the risk assessment of these chemicals.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"515 ","pages":"Article 154168"},"PeriodicalIF":4.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905991","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":"New insights into heavy metal cadmium-induced liver injury: Prominent role of programmed cell death mechanisms","authors":"Ruipeng Wang ,&nbsp;Jun Yan ,&nbsp;Honglong Zhang ,&nbsp;Xingwang Zhu ,&nbsp;Danna Xie ,&nbsp;Tingting Wang ,&nbsp;Xun Li","doi":"10.1016/j.tox.2025.154169","DOIUrl":"10.1016/j.tox.2025.154169","url":null,"abstract":"<div><div>The heavy metal cadmium (Cd) is an important environmental factor that induces liver injury and contributes to liver disease. Ongoing research aims to refine our understanding of the pathogenesis of cadmium-induced liver injury and the interactions between the various mechanisms. Oxidative stress, described as a pathophysiological basis of liver injury, is a process in which reactive oxygen species are generated, causing the destruction of hepatocyte structure and cellular dysfunction. Additionally, the activation of oxidative stress downstream signals regulates several forms of cell death, such as apoptosis, necroptosis, autophagy, ferroptosis, and pyroptosis, which significantly contributes to liver damage. Furthermore, the interplay between different types of programmed cell death highlights the complexity of liver injury mechanisms. This review summarizes the role of programmed cell death in Cd-induced liver injury and explores the relationships between different programmed cell death pathways, which is expected to provide new insights into the mechanisms of Cd-induced liver injury.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154169"},"PeriodicalIF":4.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033243","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":"Per- and polyfluoroalkyl substances as potentiators of hepatotoxicity in an exposome framework: Current challenges of environmental toxicology","authors":"Minna A Choi,&nbsp;Sophie Rose,&nbsp;Sophie Langouët","doi":"10.1016/j.tox.2025.154167","DOIUrl":"10.1016/j.tox.2025.154167","url":null,"abstract":"<div><div>Chronic liver diseases, including metabolic dysfunction-associated steatosic liver disease (MASLD) and hepatocellular carcinoma (HCC), are on the rise, potentially due to daily exposure to complex mixtures of chemical compounds forming part of the exposome. Understanding the mechanisms involved in hepatotoxicity of these mixtures is essential to identify common molecular targets that may highlight potential interactions at the molecular level. We illustrated this issue with two families of environmental contaminants, per- and polyfluoroalkyl substances (PFAS) and heterocyclic aromatic amines (HAAs), both of which could be involved in the progression of chronic liver diseases, and whose toxicity may be potentiated by interactions at the level of xenobiotic metabolism. In the study of exposome effects on chronic liver disease, New Approach Methodologies (NAMs) including omics analyses and data from various <em>in vitro</em>, <em>in vivo</em> and <em>in silico</em> approaches, are crucial for improving predictivity of toxicological studies in humans while reducing animal experimentation. Additionally, the development of complex <em>in vitro</em> human liver cell models, such as organoids, is essential to avoid interspecies differences that minimize the risk for humans. All together, these approaches will contribute to construct Adverse Outcome Pathways (AOPs) and could be applied not only to PFAS mixtures but also to other chemical families, providing valuable insights into mixture hepatotoxicity prediction in the study of the exposome. A better understanding of toxicological mechanisms will clarify the role of environmental contaminant mixtures in the development of MASLD and HCC, supporting risk assessment for better treatment, monitoring and prevention strategies.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"515 ","pages":"Article 154167"},"PeriodicalIF":4.8,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903888","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":"In vitro to in vivo extrapolation modeling to facilitate the integration of transcriptomics data into genotoxicity assessment","authors":"Anouck Thienpont ,&nbsp;Eunnara Cho ,&nbsp;Andrew Williams ,&nbsp;Matthew J. Meier ,&nbsp;Carole L. Yauk ,&nbsp;Marc A. Beal ,&nbsp;Freddy Van Goethem ,&nbsp;Vera Rogiers ,&nbsp;Tamara Vanhaecke ,&nbsp;Birgit Mertens","doi":"10.1016/j.tox.2025.154165","DOIUrl":"10.1016/j.tox.2025.154165","url":null,"abstract":"<div><div><em>In vitro</em> transcriptomics holds promise for high-throughput, human-relevant data but is not yet integrated into regulatory decision-making due to the lack of standardized approaches. For genotoxicity assessment, transcriptomic biomarkers such as GENOMARK and TGx-DDI facilitate qualitative and quantitative analysis of complex <em>in vitro</em> transcriptomic datasets. However, advancing their use in quantitative testing requires standardized methods for deriving transcriptomic Points of Departure (tPoDs) and linking them to <em>in vivo</em> responses. Herein, we investigated different approaches to calculate tPoDs and applied <em>in vitro</em> to <em>in vivo</em> extrapolation to obtain administered equivalent doses (AEDs). Human HepaRG cells were exposed for 72 h to 10 known <em>in vivo</em> genotoxicants (glycidol, methyl methanesulfonate, nitrosodimethylamine, 4-nitroquinoline-N-oxide, aflatoxin B1, colchicine, cyclophosphamide, mitomycin C, ethyl methanesulfonate, and N-Nitroso-N-ethylurea) from the highest concentration that induces up to 50 % cytotoxicity through a range of lower concentrations. Gene expression data was generated using a customized version of the TempO-Seq® human S1500 + gene panel. The GENOMARK and TGx-DDI biomarkers produced genotoxic calls for all of these reference genotoxicants. Next, we performed benchmark concentration (BMC) modeling to generate both genotoxicity-specific biomarker (tPoD_biomarkers) and generic tPoDs (tPoD _S1500+). High-throughput toxicokinetic models estimated the human AEDs for these tPoDs, which were compared with (a) previously reported genotoxicity-specific AEDs from other New Approach Methodologies, and (b) <em>in vivo</em> PoDs from animal studies. We found that the generic AEDs were more conservative than genotoxicity-specific biomarker AEDs. For six of the nine genotoxicants, transcriptomic AEDs were lower than the <em>in vivo</em> PoDs; refined kinetic models may improve predictions. Overall, <em>in vitro</em> transcriptomic data in HepaRG cells provide protective estimates of <em>in vivo</em> genotoxic concentrations, consistent with other <em>in vitro</em> genotoxicity testing systems.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"515 ","pages":"Article 154165"},"PeriodicalIF":4.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887291","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 induces the secretion of SASP factors regulated by MAPK and NF-κB signaling pathways in HEK293 cells: A possible mechanism of acute kidney damage induced by cadmium","authors":"Ziqi Ren ,&nbsp;Yuanchen Zheng ,&nbsp;Jianli Liu ,&nbsp;Zhicun Liu ,&nbsp;Jiahe Chen ,&nbsp;Haotian Liu ,&nbsp;Ruiquan Qi ,&nbsp;Huiping Ma","doi":"10.1016/j.tox.2025.154166","DOIUrl":"10.1016/j.tox.2025.154166","url":null,"abstract":"<div><div>Cadmium (Cd) is a highly toxic environmental pollutant, which can accumulate in the kidney, induce cell damage and trigger inflammatory responses. However, the specific regulation mechanism of nephrotoxicity induced by Cd remains unclear. This study was conducted to investigate the toxic effects of Cd on human embryonic kidney 293 (HEK293) cells and explore its potential mechanisms. Cell viability was assessed with MTT assay. Reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were evaluated through DCFH-DA staining and Rhodamine staining. Apoptosis was detected with Hoechst 33258 staining. The expression of the DNA damage biomarker 8-hydroxy-2’-deoxyguanosine (8-OHdG) was detected with the 8-OHdG ELISA kit. Senescence-associated secretory phenotype (SASP) factors and signaling pathways were analyzed by Western blot. The results showed that Cd exposure could induce oxidative stress and cellular inflammation. It could also impair MMP, contribute to cell apoptosis and activate MAPK and NF-κB signaling pathways. Finally, exposure to Cd triggered DNA damage and SASP production. However, NF-κB inhibitor BAY11–7082 and antioxidant NAC could inhibit these effects by suppressing NF-κB and MAPK signaling pathways. The present study revealed the specific mechanisms of Cd toxicity in HEK293 cells and provided useful information for elucidating the nephrotoxicity of Cd.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"515 ","pages":"Article 154166"},"PeriodicalIF":4.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881877","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}