IF 4.8 3区医学

Toxicology Pub Date : 2025-06-20 DOI: 10.1016/j.tox.2025.154223

Esra Mutlu, Leah Wehmas, Alison H Harrill, Michael Devito, Russell S Thomas, Michael F Hughes, Denise Macmillan, Amanda Brennan, Jackson Bounds, Chelsea A Weitekamp, Logan J Everett

{"title":"Transcriptomic dose response assessment of PFAS chemicals 3:3 fluorotelomer carboxylic acid, 7:3 fluorotelomer alcohol, and perfluorohexanesulfonamide.","authors":"Esra Mutlu, Leah Wehmas, Alison H Harrill, Michael Devito, Russell S Thomas, Michael F Hughes, Denise Macmillan, Amanda Brennan, Jackson Bounds, Chelsea A Weitekamp, Logan J Everett","doi":"10.1016/j.tox.2025.154223","DOIUrl":"https://doi.org/10.1016/j.tox.2025.154223","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFAS) are a diverse class of anthropogenic chemicals, and their widespread use in manufacturing and commerce has led to introduction of these chemicals into the environment. Owing to the lack of traditional toxicology data on the majority of PFAS, novel testing methods that provide supporting information to inform human health impacts in a relatively short time frame will be increasingly important. The US Environmental Protection Agency's (EPA) Transcriptomic Assessment Process (ETAP) was recently implemented by the Agency as an efficient and cost-effective method to begin assessing potential human health impacts of chemicals that lack traditional toxicity testing data. The method involves short-term oral dosing in male and female adult rats over a five-day interval, followed by transcriptomic dose-response assessment in twelve tissues to determine a point of departure. The ETAP point of departure identifies the dose at which there are no coordinated transcriptional changes that would indicate a potential toxicity of concern. However, this approach does not explore any specific association with hazard or mechanism. Reported here are ETAP results for three PFAS chemicals: 3:3 fluorotelomer carboxylic acid (3:3 FTCA), 7:3 fluorotelomer alcohol (7:3 FTOH), and perfluorohexanesulfonamide (PFHxSA). The transcriptomic points of departure associated with the tested chemicals, as assessed via ETAP and allometrically scaled to human equivalent doses, were 0.00235 (3:3 FTCA), 0.0152 (7:3 FTOH), and 0.00358 (PFHxSA) mg/kg-day.</p>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":" ","pages":"154223"},"PeriodicalIF":4.8,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369245","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}

引用次数: 0

Assessing the Impact of In Vitro Xenobiotic Metabolism on Estrogenic Chemical Bioactivity in High-Throughput Profiling Assays. 在高通量谱分析中评估体外外源代谢对雌激素化学生物活性的影响。

IF 4.8 3区医学

Toxicology Pub Date : 2025-06-19 DOI: 10.1016/j.tox.2025.154215

Amanda Jurgelewicz, Kristen Breaux, Clinton M Willis, Felix R Harris, Gabrielle Byrd, Joshua Witten, Derik E Haggard, Chad Deisenroth, Joshua A Harrill

{"title":"Assessing the Impact of In Vitro Xenobiotic Metabolism on Estrogenic Chemical Bioactivity in High-Throughput Profiling Assays.","authors":"Amanda Jurgelewicz, Kristen Breaux, Clinton M Willis, Felix R Harris, Gabrielle Byrd, Joshua Witten, Derik E Haggard, Chad Deisenroth, Joshua A Harrill","doi":"10.1016/j.tox.2025.154215","DOIUrl":"https://doi.org/10.1016/j.tox.2025.154215","url":null,"abstract":"<p><p>High-throughput profiling assays such as high-throughput phenotypic profiling (HTPP) with Cell Painting and high-throughput transcriptomics (HTTr) are new approach methods that have been used to characterize the bioactivity and potential hazards of chemicals. To enhance the ability to identify potential in vivo hazards during chemical screening, we previously coupled both assays to an in vitro metabolism platform, Alginate Immobilization of Metabolic Enzymes (AIME). In this study, we used the AIME platform to expand upon our previous results for three estrogenic reference chemicals by screening an additional 40 chemicals anticipated to have varied activity and/or shifts in activity with metabolism in an estrogen receptor transactivation assay (ERTA) in VM7Luc4E2 breast carcinoma cells. The results demonstrated that HTTr could detect estrogen receptor (ER) activation and identify chemicals with metabolism-induced shifts in estrogenicity via ER gene signature enrichment analysis. Additionally, HTPP could detect cases where metabolism impacted chemical cytotoxicity and cases where metabolites generated by AIME produced distinct bioactivity profiles compared to their respective parent compounds. Notably, our findings highlighted examples of chemicals that had very different phenotypic and gene expression profiles between metabolic conditions that would not be observed in traditional chemical screening in most immortalized cell line models. Incorporation of metabolism using the AIME platform into high-throughput profiling assays could help inform next generation risk assessment by providing more comprehensive hazard characterizations.</p>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":" ","pages":"154215"},"PeriodicalIF":4.8,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340423","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}

引用次数: 0

Impact of per- and polyfluoroalkyl substances structure on oxidative stress and lipid metabolism disruption in HepG2 cells 单氟烷基和多氟烷基物质结构对HepG2细胞氧化应激和脂质代谢破坏的影响。

IF 4.8 3区医学

Toxicology Pub Date : 2025-06-16 DOI: 10.1016/j.tox.2025.154218

Xue Li , Kexin Jing , Liqun He , Ping Song , Jing Yu

{"title":"Impact of per- and polyfluoroalkyl substances structure on oxidative stress and lipid metabolism disruption in HepG2 cells","authors":"Xue Li , Kexin Jing , Liqun He , Ping Song , Jing Yu","doi":"10.1016/j.tox.2025.154218","DOIUrl":"10.1016/j.tox.2025.154218","url":null,"abstract":"<div><div>Per- and polyfluoroalkyl substances (PFASs) are bioaccumulative pollutants that pose risks to ecosystems and human health, with oxidative stress and lipid metabolism disorder playing key roles in their hepatotoxicity. However, the toxicological differences between PFASs with varying chain lengths and functional groups remain unclear. This study exposed HepG2 cells to different concentrations (50, 100, 200, and 400 μM) of PFOA, PFOS, PFBA, and PFBS for 24 h to investigate their cytotoxicity and underlying mechanisms. Results indicated that all four PFASs reduced cell viability in a dose-dependent manner. Long-chain PFASs in particular, induced oxidative stress, as evidenced by elevated ROS and MDA levels. Metabolomics revealed significant alterations in lipid and amino acid metabolisms, with lipid metabolism being the most disrupted. Further analysis showed up-regulation of lipid metabolism-related genes and increased TG content, confirming these findings. Correlation analysis revealed that PFASs exacerbate oxidative stress and lipid accumulation through lipid metabolism disorders, resulting in reduced cell viability. Notably, long-chain PFASs (PFOA and PFOS) were more toxic than short-chain PFASs (PFBA and PFBS), and sulfonate-based PFASs (PFOS, PFBS) were more toxic than carboxylate-based ones (PFOA, PFBA) of similar chain length. This study provides insights into the differential toxicity of PFASs, offering a theoretical foundation for improved risk assessment and management of these compounds.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154218"},"PeriodicalIF":4.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294966","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}

引用次数: 0

Revealing toxic secrets: How PAHs accelerate cellular ageing and trigger human diseases 揭示有毒的秘密：多环芳烃如何加速细胞老化和引发人类疾病。

IF 4.8 3区医学

Toxicology Pub Date : 2025-06-16 DOI: 10.1016/j.tox.2025.154219

Yurong Wang , Peixin Xu , Hong Chen , Xin Guo , Jing Gao , Tong Wang , Dongmei Yao , Xin Li , Bingchun Liu , Jianlong Yuan

{"title":"Revealing toxic secrets: How PAHs accelerate cellular ageing and trigger human diseases","authors":"Yurong Wang , Peixin Xu , Hong Chen , Xin Guo , Jing Gao , Tong Wang , Dongmei Yao , Xin Li , Bingchun Liu , Jianlong Yuan","doi":"10.1016/j.tox.2025.154219","DOIUrl":"10.1016/j.tox.2025.154219","url":null,"abstract":"<div><div>Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants that are hazardous to human health; can be produced by a variety of pathways; and are widely present in the environment, including air, soil, and water. When PAHs enter the human body, they accelerate cellular senescence and cellular ageing by promoting cell cycle arrest, inducing the excessive production of reactive oxygen species (ROS) and DNA methylation and mitochondrial dysfunction, thereby increasing the likelihood of disease, including reproductive disorders, Alzheimer's disease and cardiovascular diseases. Therefore, studying and combatting diseases caused by PAH exposure is critical. In this work, we elaborate on the mechanism of PAH toxicity and the diseases caused by PAHs from the perspective of the cellular senescence induced by PAHs, their central component benzo(a)pyrene, and their derivatives, with the aim of elucidating the molecular mechanisms of human diseases induced by PAHs through cellular senescence to provide theoretical support for the development of targeted preventive strategies and the maintenance of public health.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154219"},"PeriodicalIF":4.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294967","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}

引用次数: 0

Three typical organophosphorus flame retardants trigger thyroid hormone synthesis by inducing oxidative stress or inflammation reactions in Nthy-ori 3‑1 cells 三种典型的有机磷阻燃剂通过诱导Nthy-ori 31 - 1细胞的氧化应激或炎症反应触发甲状腺激素合成。

IF 4.8 3区医学

Toxicology Pub Date : 2025-06-13 DOI: 10.1016/j.tox.2025.154222

Xinyu Li , Deng Pan , Yingzhen Bai , Tianrong Hang , Sibo Zhu , Zilong Hu , Biao Ma , Lihang Wang , Yuanyuan Zheng , Lijun Wu

{"title":"Three typical organophosphorus flame retardants trigger thyroid hormone synthesis by inducing oxidative stress or inflammation reactions in Nthy-ori 3‑1 cells","authors":"Xinyu Li , Deng Pan , Yingzhen Bai , Tianrong Hang , Sibo Zhu , Zilong Hu , Biao Ma , Lihang Wang , Yuanyuan Zheng , Lijun Wu","doi":"10.1016/j.tox.2025.154222","DOIUrl":"10.1016/j.tox.2025.154222","url":null,"abstract":"<div><div>Accumulating evidence shows that organophosphorus flame retardants (OPFRs) can interfere with thyroid function in animals. However, studies on the effect of OPFR exposure on human thyroid hormone (TH) synthesis remain limited and controversial. In this study, we sought to investigate the effects and mechanisms of three typical OPFRs, including Tris (2-chloroethyl) phosphate (TCEP), tris (2-butoxyethyl) phosphate (TBEP), and triphenyl phosphate (TPHP), on TH synthesis using human thyroid follicular epithelial Nthy-ori 3–1 cells. The results showed that the cytotoxicity trend toward Nthy-ori 3–1 cells was TPHP > TBEP > TCEP. Moreover, TPHP significantly increased thyroxine levels and mRNA expression of thyroid-related functional proteins including thyroid peroxidase, thyrotropin receptor, and thyroglobulin at lower concentrations compared with TCEP and TBEP. Further analysis indicated that TBEP and TCEP caused mitochondrial dysfunction and impairment of oxidative phosphorylation, thereby elevating oxidative stress, as demonstrated by increases in reactive oxygen species and lipid peroxidation. In contrast, TPHP triggered TH synthesis by mediating inflammation reactions via activation of the TNF/IL-17/MAPK signaling pathway. In conclusion, this study revealed that the three OPFRs triggered TH synthesis to varying degrees by inducing oxidative stress or inflammation reactions, providing new insights into the mechanisms of action of OPFRs on the human thyroid.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154222"},"PeriodicalIF":4.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302901","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}

引用次数: 0

Sorafenib induces intestinal toxicity by disturbing gut microbiota and activating the LPS/TLR4/NF-κB signaling pathway in mice 索拉非尼通过干扰小鼠肠道菌群和激活LPS/TLR4/NF-κB信号通路诱导肠道毒性。

IF 4.8 3区医学

Toxicology Pub Date : 2025-06-13 DOI: 10.1016/j.tox.2025.154220

Yaning Xu , Yongshi Mo , Wenxin Zhou , Meirong Qin , Meifang Li , Guo Yin , Hansheng Yu , Yuchun Chen , Haiyan Du , Yibao Jin , Houshuang Huang , Chong Ma , Jiaxuan Xia , Hao Li , Zhiyong Xie , Ping Wang , Yanjun Hong

{"title":"Sorafenib induces intestinal toxicity by disturbing gut microbiota and activating the LPS/TLR4/NF-κB signaling pathway in mice","authors":"Yaning Xu , Yongshi Mo , Wenxin Zhou , Meirong Qin , Meifang Li , Guo Yin , Hansheng Yu , Yuchun Chen , Haiyan Du , Yibao Jin , Houshuang Huang , Chong Ma , Jiaxuan Xia , Hao Li , Zhiyong Xie , Ping Wang , Yanjun Hong","doi":"10.1016/j.tox.2025.154220","DOIUrl":"10.1016/j.tox.2025.154220","url":null,"abstract":"<div><div>Sorafenib is a multitargeted tyrosine kinase inhibitor approved by the FDA as a standard first-line therapy for advanced hepatocellular carcinoma. Nevertheless, the high incidence rate of gastrointestinal (GI) adverse effects substantially limits its clinical application. The molecular mechanisms underlying the GI damage remain poorly understood. In this study, we explored the critical role of gut microbiota in sorafenib-induced intestinal toxicity using a mouse model and proposed a potential therapeutic intervention strategy. Sorafenib administration caused intestinal pathological damage, systemic inflammation, and oxidative stress in mice. Antibiotic (ABX) treatment and fecal microbiota transplantation (FMT) experiments demonstrated that the GI toxicity induced by sorafenib was mediated by the gut microbiota. 16S rRNA sequencing analysis revealed that sorafenib dramatically disturbed gut microbial homeostasis, leading to an increased abundance of Gram-negative bacteria and upregulated biosynthesis of lipopolysaccharide (LPS). Intestinal transcriptomic sequencing further indicated that sorafenib induced Gram-negative bacterial-derived LPS leakage via the compromised intestinal barrier and exacerbated inflammation via TLR4/NF-κB pathway activation. Notably, the TLR4-specific inhibitor TAK-242 effectively attenuated sorafenib-induced intestinal damage. Taken together, our study unveils a novel mechanism by which sorafenib exacerbates intestinal injury through gut microbiota dysbiosis and LPS/TLR4/NF-κB signaling pathway, while proposing TAK-242 as a promising therapeutic strategy. This study underscores the critical role of the gut microbiota in sorafenib-induced intestinal damage and offers new avenues for clinical intervention.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154220"},"PeriodicalIF":4.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302900","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}

引用次数: 0

Iron supplementation switches mode of cell death to ferroptosis during acetaminophen-induced liver injury in mice rendering it resistant to N-acetylcysteine 在对乙酰氨基酚诱导的小鼠肝损伤过程中，补铁可将细胞死亡模式切换为铁凋亡，使其对n-乙酰半胱氨酸产生抗性

IF 4.8 3区医学

Toxicology Pub Date : 2025-06-13 DOI: 10.1016/j.tox.2025.154221

Olamide B. Adelusi , Aparna Venkatraman , Jephte Y. Akakpo , Anup Ramachandran , Hartmut Jaeschke

{"title":"Iron supplementation switches mode of cell death to ferroptosis during acetaminophen-induced liver injury in mice rendering it resistant to N-acetylcysteine","authors":"Olamide B. Adelusi , Aparna Venkatraman , Jephte Y. Akakpo , Anup Ramachandran , Hartmut Jaeschke","doi":"10.1016/j.tox.2025.154221","DOIUrl":"10.1016/j.tox.2025.154221","url":null,"abstract":"<div><div>Acetaminophen (APAP) overdose can cause liver injury and is the leading cause of acute liver failure in Western countries. Hepatocellular necrosis induced by APAP involves the formation of a reactive metabolite, triggering mitochondrial oxidant stress and peroxynitrite formation. Iron-catalyzed protein nitration is critical for mitochondrial dysfunction and cell death in the absence of lipid peroxidation (LPO). However, co-treatment of APAP and ferrous sulfate aggravated protein nitration and liver injury but also triggered extensive LPO (measured as malondialdehyde and hydroxy eicosatetraenoic acid (HETE) species). The objective of this study was to evaluate whether the aggravated injury under these conditions is caused by a combination of protein nitration and LPO or if LPO is now the dominant injury mechanism. To test this, C57BL/6 J mice were co-treated with APAP (300 mg/kg) and a moderate dose of ferrous sulfate (0.15 mmol/kg) for 6 h. Some animals also received a dose of Mito-TEMPO, the mitochondria-targeted SOD mimetic, or minocycline, an inhibitor of mitochondrial iron uptake. Although Mito-TEMPO and minocycline eliminated protein nitration and liver injury after APAP alone, these interventions did not affect LPO and only had a moderate effect on protein nitration and liver injury in the APAP+Fe<sup>2</sup><sup>+</sup> group, suggesting LPO as the main mechanism of cell death. Consistent with these findings, delayed treatment with clinically relevant antidotes N-acetylcysteine and fomepizole did not reduce LPO or liver injury. Thus, liver injury after APAP+Fe<sup>2+</sup> is no longer primarily driven by mitochondrial oxidant stress and peroxynitrite-mediated necrosis but by lipid peroxidation and a ferroptosis-like cell death.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154221"},"PeriodicalIF":4.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144291081","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}

引用次数: 0

Gut microbiome contributes to 6PPD-quinone induced cognitive impairment through PI3K/Akt signaling 肠道微生物组通过PI3K/Akt信号通路参与6ppd -醌诱导的认知障碍。

IF 4.8 3区医学

Toxicology Pub Date : 2025-06-11 DOI: 10.1016/j.tox.2025.154217

Xiaozhou Zhu , Yaqiu Xu

{"title":"Gut microbiome contributes to 6PPD-quinone induced cognitive impairment through PI3K/Akt signaling","authors":"Xiaozhou Zhu , Yaqiu Xu","doi":"10.1016/j.tox.2025.154217","DOIUrl":"10.1016/j.tox.2025.154217","url":null,"abstract":"<div><div>Studies show that N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPD-Q) accumulates in the central nervous system, but its role in cognitive impairment and underlying mechanisms remain unclear. Morris water maze assay revealed that 6-PPDQ significantly impairs cognitive function, particularly learning and memory. HE staining revealed alterations in the hippocampal DG and CA3 regions of exposed mice, including sparse cell arrangement, blurred boundaries, nuclear condensation, and a reduction in Nissl bodies. Fecal microbiota transplantation from 6-PPDQ-exposed mice to normal mice induced cognitive deficits and hippocampal pathological damage. Western Blot assay showed that 6-PPDQ exposure resulted in inhibition of PI3K/AKT signaling. Moreover, blunted PI3K/AKT signaling was observed in mice transplanted with 6-PPDQ-associated mice fecal microbiota. Further analysis of 16S rDNA assay identified a total of 30 differential bacteria at the genus level, including 8 upregulated bacteria such as g_Helicobacter and 22 downregulated bacteria such as g_Prevotellaceae_NK3B31_group. In conclusion, this study uncovers gut microbiome mediates 6PPD-Q-induced cognitive impairment through inhibiting of PI3K/Akt signaling, and provides a basis for further investigation into gut microbiome's protective effects on 6-PPDQ-induced nervous system injury.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154217"},"PeriodicalIF":4.8,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286540","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}

引用次数: 0

Role of neuroglia cell-derived microvesicles in cobalt chloride-induced mitochondrial autophagy in neurons 神经胶质细胞来源的微泡在氯化钴诱导的神经元线粒体自噬中的作用。

IF 4.8 3区医学

Toxicology Pub Date : 2025-06-07 DOI: 10.1016/j.tox.2025.154214

Husheng Li , Fuli Zheng , Wenya Shao , Guangxia Yu , Hong Hu , Zhenkun Guo , Siying Wu , Ying Tang , Huangyuan Li

{"title":"Role of neuroglia cell-derived microvesicles in cobalt chloride-induced mitochondrial autophagy in neurons","authors":"Husheng Li , Fuli Zheng , Wenya Shao , Guangxia Yu , Hong Hu , Zhenkun Guo , Siying Wu , Ying Tang , Huangyuan Li","doi":"10.1016/j.tox.2025.154214","DOIUrl":"10.1016/j.tox.2025.154214","url":null,"abstract":"<div><div>The extensive use of cobalt resources has significantly increased the risk of cobalt contamination globally, with cobalt chloride posing a serious environmental and health concern. Although previous studies have shown that extracellular vesicles play a key role in intercellular communication, the mechanisms by which extracellular vesicles derived from neuroglia cells affect neuronal cells remain poorly understood. This study aimed to investigate whether microvesicles produced by neuroglia cells could mitigate cobalt chloride-induced neuronal damage and to explore the underlying mechanisms. Our results revealed that cobalt chloride induces cytotoxicity in HT22 and MN9D neuronal cells. A 24-hour cobalt chloride treatment triggered mitochondrial autophagy in both cell types and disrupted their mitochondrial dynamics. Further analysis showed that microvesicles secreted by GL261 neuroglia cells were taken up by both types of neuronal cells. Notably, the uptake of GL261-derived microvesicles by MN9D cells inhibited autophagy and restored mitochondrial membrane potential and reactive oxygen species levels. In conclusion, our findings highlight the critical role of neuroglia cell-derived microvesicles in cobalt chloride-induced neuronal toxicity and offer potential new targets and strategies for the prevention and treatment of cobalt chloride toxicity.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154214"},"PeriodicalIF":4.8,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259010","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}

引用次数: 0

Next generation risk assessment and new approach methodologies for safe and sustainable by design chemicals and materials: Perspectives and challenges for occupational health 新一代风险评估和设计化学品和材料的安全和可持续的新方法：职业健康的观点和挑战。

IF 4.8 3区医学

Toxicology Pub Date : 2025-06-07 DOI: 10.1016/j.tox.2025.154211

Veruscka Leso , Bernd Nowack , Achilleas Karakoltzidis , Fotini Nikiforou , Spyros Karakitsios , Denis Sarigiannis , Ivo Iavicoli

{"title":"Next generation risk assessment and new approach methodologies for safe and sustainable by design chemicals and materials: Perspectives and challenges for occupational health","authors":"Veruscka Leso , Bernd Nowack , Achilleas Karakoltzidis , Fotini Nikiforou , Spyros Karakitsios , Denis Sarigiannis , Ivo Iavicoli","doi":"10.1016/j.tox.2025.154211","DOIUrl":"10.1016/j.tox.2025.154211","url":null,"abstract":"<div><div>Europe is facing increasingly challenging threats to health and well-being, including chemical pollution, climate change, and biodiversity loss. To counter such threats, the European Union has developed a series of policy strategies, including the Chemicals Strategy for Sustainability and the Zero Pollution Action Plan that pointed out the need for safe-and-sustainable-by-design (SSbD) chemicals/materials. The SSbD and the “zero pollution” ambition will inevitably lead to a transformation of the conditions of exposure to chemicals both in general living environments and workplaces with the consequent need to adequately anticipate and manage the chemical risk, starting from the assessment of the hazard and risk characterization. Among those, next generation risk assessment (NGRA) is defined as a human-relevant, exposure-led, hypothesis driven risk assessment approach, designed to prevent harm. To date, application of NGRA has been restricted to assessing the use of cosmetics, and it has not been implemented in occupational risk assessment. Occupational safety assessment represents an area that would benefit from increasing application of NGRA to safety decision making. Additionally, the application of new approach methodologies (NAMs) can support the generation of data useful to implement the operationalization of the SSbD framework, favorably impacting the adoption of suitable management strategies. In turn, the historical occupational preventive and protective approach to the health and safety of workers may provide support to adequately implement NGRA in the occupational context. Therefore, this work aims to provide an overview on the principal available NAMs and their possible implications for occupational chemical risk assessment and management.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154211"},"PeriodicalIF":4.8,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259009","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}

引用次数: 0

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