Ecotoxicology and Environmental Safety最新文献

{"title":"Urinary phthalate exposure in relation to plasma neurofilament light chain and cognitive function among older adults: Repeated-measures and cross-sectional analyses.","authors":"Xin Xu, Jianheng Zheng, Jing Li, Long Zhao, Jianguo Yu, Bo Chen, Zhenyu Xie, Nan Yang, Ying Qing, Ruihua Dong","doi":"10.1016/j.ecoenv.2026.120941","DOIUrl":"https://doi.org/10.1016/j.ecoenv.2026.120941","url":null,"abstract":"<p><p>Phthalates (PAEs) are ubiquitous neurotoxic contaminants, but their effects on cognitive function in the elderly remain unclear. In this study, we explored the associations between repeated urinary PAE measurements and plasma neurofilament light chain (NfL) levels, as well as cognitive function among older adults in Shanghai. Ten urinary PAE metabolites were measured in 330 participants in 2019, 2021, and 2023. Plasma NfL was measured and the Mini-Mental State Examination (MMSE) was administered during the third survey wave. A complementary cross-sectional analysis included 1020 participants assessed in 2023. Both single-pollutant and mixture models were applied. In the repeated-measures analysis, the 2021 PAE mixture (β = 0.071; 95% CI: 0.005, 0.138) and the joint mixture across all three waves (β = 0.096; 95% CI: 0.003, 0.189) were associated with higher NfL levels. No significant associations with MMSE outcomes were observed in the smaller cognitive subsample. In the 2023 analysis, the PAE mixture was associated with higher NfL levels, lower orientation, registration, and total MMSE scores, and higher odds of cognitive impairment. These findings suggest that the associations with NfL may vary according to the timing of exposure assessment and provide complementary cross-sectional evidence linking PAE exposure to selected cognitive outcomes. Further prospective studies are needed to confirm these findings.</p>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"325 ","pages":"120941"},"PeriodicalIF":6.6,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tebuconazole-induced ferroptosis impairs human trophoblast function via GPX4: A multi-omics study on unexplained recurrent pregnancy loss.","authors":"Shaowei Wang, Huiyi Che, Xiya Ren, Zi Lin, Zhuoqi Chen, Yang Zhu, Jingyun Chen, Yunbing Tang, Ren-Shan Ge, Yingfen Ying","doi":"10.1016/j.ecoenv.2026.120943","DOIUrl":"https://doi.org/10.1016/j.ecoenv.2026.120943","url":null,"abstract":"<p><p>Tebuconazole (TEB) is a widely used triazole fungicide with suspected endocrine-disrupting and reproductive toxicity. However, its effects on human placental trophoblasts and its association with unexplained recurrent pregnancy loss (RPL) remain poorly defined. Chorionic villi from 27 women with unexplained RPL and 25 women with normal pregnancies were analyzed by HPLC-MS/MS, and TEB effects were examined in BeWo and HTR-8/SVneo trophoblasts. Villus TEB residues were 1.82-fold higher in the RPL group (mean 0.0356 versus 0.0196 ng/g; P < 0.001), whereas TEB-OH did not differ significantly. In HTR-8/SVneo cells, 48-h TEB exposure reduced estradiol secretion at 20-80 µM and impaired migration at 40-80 µM without a significant loss of CCK-8 viability, and increased intracellular labile Fe^2 +. Transcriptome profiling at 80 µM identified 1680 differentially expressed genes (797 up-regulated, 883 down-regulated), and the downregulation of GPX4, TFRC, and SLC40A1 was confirmed by RT-qPCR and Western blotting. Network toxicology identified 72 core targets shared with RPL and fetal growth restriction, and docking predicted GPX4 as a candidate binding target of TEB (Ki= 44.74 µM). Consistent with a ferroptotic mechanism, ferrostatin-1 (2 µM) attenuated TEB-induced lipid peroxidation and Fe²⁺accumulation and partially restored GPX4, SLC40A1, and TFRC abundance, trophoblast migration, and estradiol secretion. These findings suggest that ferroptosis-related lipid peroxidation contributes to TEB-induced trophoblast dysfunction and links chorionic villus TEB residues to unexplained RPL. Because the effective in vitro concentrations exceed typical human exposure levels, the results provide mechanistic evidence of hazard and warrant further risk assessment.</p>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"325 ","pages":"120943"},"PeriodicalIF":6.6,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ozone exposure and ferroptosis: Mechanistic links and current evidence.","authors":"Wenyi Liao, Zhigang Li, Yongjie Wei, Teng Wang","doi":"10.1016/j.ecoenv.2026.120942","DOIUrl":"https://doi.org/10.1016/j.ecoenv.2026.120942","url":null,"abstract":"<p><p>Ambient ozone (O₃) is a highly reactive secondary air pollutant whose health relevance is increasingly recognized. Although epidemiological evidence has linked O₃ exposure to multiple diseases, the biological mechanisms underlying the health effects remain incompletely understood. Ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation, has been implicated in diverse diseases and is increasingly considered a potential mechanism underlying pollutant-induced health injury. Notably, the core biochemical features of ferroptosis closely align with multiple O₃-induced molecular responses, including reactive oxygen species accumulation, excessive lipid peroxidation, and impaired antioxidant defenses, suggesting that ferroptosis may be a regulated cell death mechanism involved in O₃-related toxicity. However, evidence linking O₃ exposure to ferroptosis remains limited and fragmented. Therefore, this review synthesizes current mechanistic insights and available evidence connecting O₃ exposure with ferroptosis. Relevant literature was retrieved from databases including PubMed, Web of Science, and Scopus, covering studies published up to May 2026, and included studies addressing O₃ exposure in relation to ferroptosis, or to ferroptosis-relevant processes such as lipid peroxidation, antioxidant disruption, iron dyshomeostasis, or mitochondrial dysfunction. We further discuss current limitations and priorities for future research, with the aim of evaluating ferroptosis as a candidate mechanism underlying O₃-associated health effects.</p>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"325 ","pages":"120942"},"PeriodicalIF":6.6,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149214869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polystyrene nanoplastics trigger ferroptosis-dependent liver injury caused by ACSL4 overaccumulation.","authors":"Jiawen Tao, Yi Liu, Ping Deng, Jia Xie, Min Lin, Lingling Yang, Siyu Chen, Chunhai Chen, Huifeng Pi, Zhengping Yu","doi":"10.1016/j.ecoenv.2026.120937","DOIUrl":"https://doi.org/10.1016/j.ecoenv.2026.120937","url":null,"abstract":"<p><p>Nanoplastics (NPs) are persistent environmental pollutants that can accumulate in the liver, but the mechanisms of their hepatotoxicity remain poorly understood. Here, using AML12 cells and a mouse model, we investigated how polystyrene nanoplastics (PS-NPs) cause liver injury. Exposure to PS-NPs induced dose-dependent cytotoxicity and ferroptosis, evidenced by elevated Fe²⁺ and reactive oxygen species (ROS) levels, enhanced lipid peroxidation, glutathione peroxidase 4 (GPX4) downregulation, and acyl-CoA synthetase long chain family member 4 (ACSL4) upregulation. PS-NPs exposure increased hepatic pathological injury scores and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in vivo. Treatment with ferrostatin-1 (Fer-1) markedly attenuated these changes. Mechanistically, PS-NPs exposure disrupted lysosomal function, as shown by reduced expression of lysosome-associated membrane proteins and increased lysosomal pH. This lysosomal impairment hindered degradative capacity and led to ACSL4 accumulation. Restoring lysosomal function with NKH477 reduced ACSL4 levels. Together, these findings suggest that PS-NPs promote hepatocyte ferroptosis through lysosomal dysfunction and subsequent ACSL4 accumulation. This study provides new insight into the mechanisms of PS-NPs-induced liver toxicity and highlights potential targets for intervention.</p>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"325 ","pages":"120937"},"PeriodicalIF":6.6,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149214938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasticizers induce central precocious puberty via dysregulation of EGFR/MYC/PTEN/mTOR-mediated HPG axis activation.","authors":"Lixue Ouyang, Yu Yan, Haodongfang Zhang, Fan Yang","doi":"10.1016/j.ecoenv.2026.120869","DOIUrl":"https://doi.org/10.1016/j.ecoenv.2026.120869","url":null,"abstract":"<p><p>The incidence of central precocious puberty (CPP) has been steadily increasing, and plasticizers have been implicated in the onset of CPP. A thorough understanding of these mechanisms could enable early intervention to prevent CPP from its root cause, offering valuable directions for future basic research and treatment strategies. This study identified CPP-relevant targets for plasticizers via public databases, screening biomarkers with eight algorithms. Furthermore, GeneMANIA network analysis, chromosome localization, subcellular localization, ceRNA network analysis, and functional enrichment analysis were included to ascertain the molecular function of biomarkers. Molecular docking and molecular dynamics analyses provided valuable insights into ligand-target interaction mechanisms. A DEHP-induced CPP mouse model was validated by morphological, histological, hormonal, and molecular markers. EGFR, MYC, PTEN and MTOR were identified as CPP biomarkers, involved in cell cycle regulation and PI3K/AKT signaling. These targets were enriched in stress responses and cancer-related pathways. EGFR exhibited the broadest plasticizer binding spectrum, with EGFR-butyl benzyl phthalate showing the highest binding affinity (-8.0 kcal/mol); molecular dynamics confirmed stable target-plasticizer complexes. The DEHP-induced CPP model was successfully established, with model mice exhibiting an advanced vaginal opening time, increased absolute weights and indices of ovaries and uterus, accelerated estrous cycles, altered ovarian follicle developmental phenotypes, elevated serum FSH/LH/E2 (p < 0.001) and dysregulated biomarker expression (downregulated PTEN, upregulated EGFR/MYC/MTOR) in the HPG axis. The increased expression of canonical pubertal regulators indicates premature activation of the KNDy/kisspeptin-GnRH neuroendocrine axis in DEHP-induced CPP. Our study identified EGFR, MYC, PTEN and mTOR as core targets of plasticizer-triggered CPP, clarifying their regulatory mechanisms and providing novel molecular insights for CPP management.</p>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"325 ","pages":"120869"},"PeriodicalIF":6.6,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149214901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methylmercury accumulation patterns in Coix lacryma-jobi L. and its associated human exposure risks.","authors":"Mingtu Ma, Xiaohang Xu, Xiaomin Yang, Jialiang Han, Fangfang Zou, Le Wang, Ran Li, Guangle Qiu, Zhongxuan Liang, Minghao Liao, Yonggui Wu, Hongye Wan, Manman Wu, Md Habibullah-Al-Mamun, Pan Wu","doi":"10.1016/j.ecoenv.2026.120931","DOIUrl":"https://doi.org/10.1016/j.ecoenv.2026.120931","url":null,"abstract":"<p><p>Mercury (Hg) pollution endangers the environment and human health. Coix (Coix lacryma-jobi L.), an important medicinal and edible crop, requires study of its Hg, particularly methylmercury (MeHg) accumulation characteristics and exposure risks. Paired coix plants and rhizosphere soils were collected from cultivation areas in Southwest China to assess inorganic Hg (IHg) and MeHg distribution and transfer in root, stem, leaf and grain. Combined with partial least squares path modeling (PLS-PM), we quantified the effects of soil properties, bioavailable Hg fractions, and dissolved organic carbon on Hg transportation and accumulation in the soil-coix system. Across tissues, MeHg exhibited stronger bioconcentration than IHg. Approximately 55% of coix grain samples had MeHg bioconcentration factors (BCFs) exceeding 1 (mean = 3.44, comparable to MeHg-sensitive rice); coix grain accumulated MeHg, yet its MeHg concentration (0.281 ± 0.215 µg/kg) remained lower than rice from heavily Hg-contaminated sites. The positive correlations of MeHg concentrations between coix grain and leaf (p < 0.05), and particularly between leaf and rhizosphere soil (p < 0.001), suggest that rhizosphere soil is the primary source of MeHg accumulated in coix grain. In contrast, leaf IHg levels (61.3 ± 46.7 µg/kg) were significantly higher than those in stem and root tissues, and the IHg translocation factors (TFs) from root to aboveground tissues were low. Dietary coix intake was the primary Hg exposure pathway for residents. Although the non-carcinogenic hazard quotients for residents were below the safety threshold (HQ < 1), children faced greater IHg and MeHg health risks. This study is the first to clarify the differential accumulation mechanisms of IHg and MeHg in coix, and informs safe coix production, soil Hg monitoring, and dietary Hg risk management.</p>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"325 ","pages":"120931"},"PeriodicalIF":6.6,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149214933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Data-driven prediction of heavy metal bioconcentration factors in sunflower: A multifactor modeling study","authors":"Chongchong Qi,&nbsp;Xin Huang,&nbsp;Wenqi Jiao,&nbsp;Xinhang Xu,&nbsp;Tao Hu","doi":"10.1016/j.ecoenv.2026.120866","DOIUrl":"10.1016/j.ecoenv.2026.120866","url":null,"abstract":"<div><div>Heavy metal (HM) contamination of soil threatens food security and ecosystem health. Sunflower phytoextraction is an environment-friendly option for managing contaminated soil. However, formulating phytoremediation strategies requires a reliable prediction of the bioconcentration factor (BCF) of HMs in sunflower, which remains difficult because of the nonlinear, multifactor controls on HM uptake, and sparse and incomplete datasets. In this study, we developed a machine learning (ML) framework to predict the BCF of HMs in sunflower. Multiple ML models combined with various data preprocessing techniques were systematically evaluated to identify an optimal modeling approach. The optimal categorical boosting model achieved a mean coefficient of determination of 0.60 on the test set, demonstrating satisfactory predictive performance and robust generalization to unseen data. Shapley additive explanation analysis identified soil HM concentration, sunflower components, and electronegativity as dominant predictors. Partial dependence plots further revealed a decreasing trend in BCF with increasing soil HM concentrations. Moreover, structural equation modeling suggested that variation in BCF was primarily associated with direct effects of HM and soil properties, while soil properties also played an important mediating role. These findings provide a transferable framework for BCF prediction and practical guidance for optimizing sunflower-based phytoremediation strategies across diverse HMs and soil conditions.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"325 ","pages":"Article 120866"},"PeriodicalIF":6.6,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal fipronil sulfone exposure is associated with altered fetal liver-function biomarkers: Evidence integrating epidemiology, network toxicology, and molecular docking","authors":"Chi Zhang,&nbsp;Xianfeng Yue,&nbsp;Haitao Zhang,&nbsp;Xuan Wang,&nbsp;Jing Zhan,&nbsp;Jiaying Liu,&nbsp;Xuezhen Zhao,&nbsp;Dong Li,&nbsp;Jingguang Li,&nbsp;Dawei Chen","doi":"10.1016/j.ecoenv.2026.120923","DOIUrl":"10.1016/j.ecoenv.2026.120923","url":null,"abstract":"<div><div>Fipronil and its metabolites (FPM) are widely detected in environmental and biological matrices, but human evidence of developmental hepatotoxicity remains scarce. We quantified six fipronil-related compounds, five liver-function biomarkers, and four inflammatory cytokines in umbilical cord serum from 187 neonates. Fipronil sulfone was detected in all samples (median: 101.6 pg/mL). In covariate-adjusted linear models, each 10-fold increase in fipronil sulfone was associated with higher alanine aminotransferase (ALT) [<em>β</em> = 3.73, 95% <em>CI</em>: (1.58–5.88)], aspartate aminotransferase (AST) [<em>β</em> = 13.13, 95% <em>CI</em>: (2.15–24.12)], gamma-glutamyl transferase (GGT) [<em>β</em> = 51.50, 95% <em>CI</em>: (3.74–99.25)], and alkaline phosphatase (ALP) [<em>β</em> = 93.52, 95% <em>CI</em>: (44.61–142.44)]. The associations with ALT and ALP remained statistically significant after FDR correction. Bayesian kernel machine regression and machine-learning models consistently prioritized fipronil sulfone as an important mixture component associated with these biomarkers. Exploratory BBMD analysis estimated benchmark concentrations associated with a 10% change in liver-function biomarkers. Mediation analyses indicated that interleukin-1β partially mediated the associations with ALT and AST (16.25% and 19.75%, respectively), whereas tumor necrosis factor-α mediated the associations with ALT, AST, and ALP (11.21%-20.91%). Network toxicology highlighted inflammatory, oxidative-stress, PI3K-Akt, MAPK, and TNF signaling pathways, and molecular docking predicted favorable binding of fipronil sulfone to TNF, ALB, and INS. These findings associate cord-serum fipronil sulfone concentrations with altered cord-serum liver biomarkers and identify inflammatory signaling as a potential intermediate pathway. Longitudinal and experimental studies are needed to confirm temporality and biological causation.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"325 ","pages":"Article 120923"},"PeriodicalIF":6.6,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large-scale plasma metabolic profiling identifies signatures and biomarkers associated with air pollution and arrhythmias: A prospective cohort study from UK Biobank","authors":"Hongguang Wu,&nbsp;Nan He,&nbsp;Peiyao Li,&nbsp;Juda Hu,&nbsp;Jing Chen,&nbsp;Xiaohong Li,&nbsp;Xiangming Hu,&nbsp;Yangning Zhang,&nbsp;Jin Bu,&nbsp;Ye Ma,&nbsp;Alwadi Yazan,&nbsp;Petros Koutrakis,&nbsp;Feiying He,&nbsp;Yanqiu Ou","doi":"10.1016/j.ecoenv.2026.120919","DOIUrl":"10.1016/j.ecoenv.2026.120919","url":null,"abstract":"<div><h3>Background</h3><div>Air pollution is an established modifiable risk factor for cardiac arrhythmia, yet the metabolic mechanisms underlying this association remain poorly understood. This study aimed to elucidate how air pollutants promote arrhythmias through metabolic pathway perturbations.</div></div><div><h3>Methods</h3><div>We conducted a prospective analysis of 449,068 UK Biobank participants without baseline arrhythmia. Exposures to PM_2.5, PM₁₀, NO₂, and NO_x were assessed using land use regression models. Plasma metabolomic profiling including 170 metabolites via 1H-NMR was performed at baseline. Elastic net regression, Cox proportional hazards models, and mediation analysis were employed to identify pollutant-associated metabolic signatures, quantify their mediating effects, and characterize pathway enrichment across different kinds of arrhythmias.</div></div><div><h3>Results</h3><div>During a median follow-up of 16.31 years, a total of 47,381 arrhythmia cases were identified. All four pollutants were prospectively associated with increased arrhythmia risk (hazard ratios ranged from 1.015 to 1.257 per 10 μg/m³). The derived metabolomic signatures significantly mediated these associations between different air pollutants and arrhythmia (mediation proportions: PM_2.5-related, 11.19%; PM₁₀-related, 5.19%; NO₂-related, 7.44%; NO_x-related, 9.82%). Pathway enrichment analysis consistently identified lipid metabolism, ketone body metabolism, and amino acid metabolism as core affected pathways. Notably, compared to atrial fibrillation and supraventricular tachycardia, the ketone body metabolic pathway appeared to account for a larger proportion of the association with intraventricular block.</div></div><div><h3>Conclusions</h3><div>This study suggests that air pollution increases arrhythmia risk through distinct, subtype-specific metabolic perturbations, providing novel insights into the metabolic pathways linking environmental pollutants to different arrhythmia subtypes.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"325 ","pages":"Article 120919"},"PeriodicalIF":6.6,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tributyl phosphate induces liver aging via fumarate-mediated mitochondrial DNA escape triggered FPR2 activation","authors":"Liwei Yang,&nbsp;Honghao Qian,&nbsp;Zhili Ge,&nbsp;Tianyou Wang,&nbsp;Jiaxin Zhang,&nbsp;Jingjing Shi,&nbsp;Huibin Jiang,&nbsp;Xinyu Zhang,&nbsp;Yuebin Lv,&nbsp;Liting Zhou","doi":"10.1016/j.ecoenv.2026.120885","DOIUrl":"10.1016/j.ecoenv.2026.120885","url":null,"abstract":"<div><h3>Background</h3><div>Liver aging–induced failure and dysfunction in other organs constitute a critical aging phenotype that is distinct from chronological aging. Unlike intrinsic aging, hepatic senescence is predominantly driven by environmental factors. Tributyl phosphate (TBP) was identified as a potential key environmental trigger of liver aging; however, the underlying mechanisms remain largely elusive.</div></div><div><h3>Methods</h3><div>Rats and BRL-3A cells were treated with TBP. Serum metabolomics, liver proteomics, hepatocyte ultrastructure, β-galactosidase (β-GAL) activity, cell cycle progression, ROS and senescence-associated secretory phenotype (SASP) levels, as well as protein related to chromatin remodeling and DNA damage were used to evaluate liver aging. WRW4, ethidium bromide (EB), Lv-FH and monomethyl fumarate were utilized respectively to establish models of FPR2 inhibition, cytoplasmic mitochondrial DNA (mtDNA) depletion. fumarate clearance and supplied supplementation.</div></div><div><h3>Results</h3><div>TBP induced cell cycle arrest, increased β-GAL activity, and elevated ROS and MMP-1 levels while upregulating p53, lys9, and γ-H2A.X protein expression. Additionally, TBP inhibited HP1 protein expression in rat livers and cells(<em>P</em> &lt; 0.05). Significant changes in metabolites and proteins following TBP exposure were enriched in aging-related pathways. After treating with, WRW4, EB, Lv/sh-FH and monomethyl fumarate respectively, these changes were all reversed in BRL-3A cells (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>This study elucidat the effect of fumarate-mediated mtDNA escape in liver aging induced by TBP. We found that exposure to TBP induces the levels of fumarate, which directly drives mtDNA escape and activates the FPR2, finally triggers liver aging of rats.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"325 ","pages":"Article 120885"},"PeriodicalIF":6.6,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}