Xinru Wang , Chengmin Zha , Zihan Wang , Wenwen Fan , Chenyang Ji , Xinzhong Zhang , Zongmao Chen , Fengjian Luo , Li Zhou
{"title":"Defense mechanism of tea plant (Camellia sinensis L.) to tolfenpyrad reveals emerging role of melatonin in pesticide residue control","authors":"Xinru Wang , Chengmin Zha , Zihan Wang , Wenwen Fan , Chenyang Ji , Xinzhong Zhang , Zongmao Chen , Fengjian Luo , Li Zhou","doi":"10.1016/j.ecoenv.2025.117916","DOIUrl":"10.1016/j.ecoenv.2025.117916","url":null,"abstract":"<div><div>Excessive use of pesticides has raised great concern on food safety as well as crop quality in the form of pesticide residues. Plants have natural defense mechanisms against pesticides for its alleviation. This study investigated distribution of tolfenpyrad as well as physiological, metabolomic, transcriptomic and hormonal responses of tea plants to tolfenpyrad application. Results show that tolfenpyrad tends to accumulate in tea leaves, with limited translocation to stems and roots after foliar application. While no significant change in plant biomass or growth status was apparent following tolfenpyrad application, it triggered reactive oxygen species (ROS) and antioxidant system impacts. Metabolomic and transcriptomic analyses reveal disrupted purine metabolism and nitrogen metabolism, mainly in amino acid pathways, with a glutathione (GSH) detoxification response. Hormonal and targeted metabolic profiling confirms a significant elevation in melatonin biosynthesis, then exogenous application of melatonin is proved to efficiently reduce pesticide residue in tea plants. This study improved our understanding of the tea plants’ defense mechanism to pesticide, and suggested an emerging plant-derived regulator for improving quality and safety of tea products.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"292 ","pages":"Article 117916"},"PeriodicalIF":6.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509009","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}
Jian Zhang , Cong Liu , Juan Ling , Weiguo Zhou , Youshao Wang , Hao Cheng , Xiaofang Huang , Qingsong Yang , Wenqian Zhang , Tongyin Liang , Ying Zhang , Junde Dong
{"title":"Revealing the potential of biochar for heavy metal polluted seagrass remediation from microbial perspective","authors":"Jian Zhang , Cong Liu , Juan Ling , Weiguo Zhou , Youshao Wang , Hao Cheng , Xiaofang Huang , Qingsong Yang , Wenqian Zhang , Tongyin Liang , Ying Zhang , Junde Dong","doi":"10.1016/j.ecoenv.2025.117991","DOIUrl":"10.1016/j.ecoenv.2025.117991","url":null,"abstract":"<div><div>Seagrass meadows are under threat due to climate change and human activities, including heavy metal contamination, which can accumulate in seagrass tissues and harm their health and productivity. Despite extensive research, effective remediation strategies are lacking. This study investigated biochar's potential as a remediation agent for seagrass meadows affected by heavy metal pollution. Heavy metal pollution was simulated by adding copper (Cu) and chromium (Cd) to seagrass <em>Thalassia hemprichii</em>, and the remediation effects of biochar were evaluated by monitoring seagrass physiology, root-associated microbial communities, and heavy metal concentrations. Seagrasses can accumulate heavy metals, which adversely affect their health and alter microbial communities. Seagrasses may resist heavy metal stress by releasing dissolved organic carbon (DOC) and recruiting beneficial bacteria. Biochar reduced heavy metal bioavailability and restored seagrass ecosystem health, as evidenced by restored microbial community dynamics. This study highlights biochar's promising role in seagrass meadow restoration impacted by heavy metal pollution.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"292 ","pages":"Article 117991"},"PeriodicalIF":6.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534767","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":"Unraveling fishers' perceptions: Impact of mining on fish yield and diversity in Mwenga, South Kivu, Eastern Democratic Republic of Congo","authors":"Dieudonné Shukuru Wasso , Daud Kassam , Adolphe Kwakanaba Mweze , Socrate Kamani Tungidi , Emmanuel Tulinabo Ahanyirwe , Christian Masumbuko Baraka , Rodrigue Balthazar Basengere Ayagirwe","doi":"10.1016/j.ecoenv.2025.117953","DOIUrl":"10.1016/j.ecoenv.2025.117953","url":null,"abstract":"<div><div>In South Kivu province, Eastern Democratic Republic of Congo, a significant number of active mines are situated near strictly protected ecosystems, where adverse effects including deforestation, water pollution, soil degradation and loss of biodiversity have been documented. Understanding the local communities' perceptions of how mining affects fish diversity and yield is crucial for fostering a harmonious relationship among stakeholders and preserving the environment and its biodiversity, particularly in Mwenga territory where mining activities are widespread. This study aimed to establish the typology of fishers, and to investigate their perceptions and drivers of these perceptions regarding the impact of mining operations on fish yield and diversity in the Mwenga territory, Democratic Republic of Congo. A cross-sectional survey involving 75 randomly selected fishers was conducted, and data were collected through structured questionnaires. Water quality parameters were measured at three different monitoring sites along the Zalya-Elila River, a primary watercourse in the Mwenga territory. Principal component analysis identified two distinct groups of fishers. Key factors influencing the diversity of Mwenga fishers included age, household size, monthly income, fishing experience, number of fish caught daily 15 years ago, distance between the river and the mine site, fishing hours per day, weekly fishing frequency, and quantity (weight) of fish caught per day currently and 15 years ago (p < 0.05). A significant proportion (39.02 %) of surveyed fishers reported a decline in fish diversity due to mining activities, with only seven out of the 13 previously present fish species remaining in the study area. Moreover, the average catch per fisher per day decreased from 9.00 ± 4.20 Kg 15 years ago to 4.45 ± 1.88 Kg currently. Various factors influenced fishers' perceptions, including age, marital status, education level, household size, comparison of current and past fish catches, presence of nearby mining sites, fishing hours per day, pollution, interconnections between water bodies, and the sediment presence in water bodies (p < 0.05). Among the 11 water parameters monitored, only the temperature, dissolved oxygen, biological oxygen demand over five days, chlorite concentration, sulfate, and nitrate met acceptable and desirable ranges for fish in natural ecosystems. The information obtained from this study constitutes a prerequisite for developing and implementing studies or policies aimed at mitigating and combatting the negative effects of mining on fish yield and diversity in the Mwenga territory. Actions and policies are needed from local authorities to ensure the sustainability of fish biodiversity in the Mwenga territory.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"292 ","pages":"Article 117953"},"PeriodicalIF":6.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534769","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}
Bin Liu , Xue Zhao , Hongqi He , Linwei Zhou , Yuhan Fan , Xu Chai , Xin Xu , Xinjie Gong , Shuli An , Xiaodong Ling , Xia Chu
{"title":"Exposure to urinary polycyclic aromatic hydrocarbon metabolites for the effect of lung function among children and adolescents: Epidemiological study and mechanism exploration","authors":"Bin Liu , Xue Zhao , Hongqi He , Linwei Zhou , Yuhan Fan , Xu Chai , Xin Xu , Xinjie Gong , Shuli An , Xiaodong Ling , Xia Chu","doi":"10.1016/j.ecoenv.2025.117990","DOIUrl":"10.1016/j.ecoenv.2025.117990","url":null,"abstract":"<div><div>Human are widely exposed to polycyclic aromatic hydrocarbon (PAHs), but existing evidence about exposure to urinary PAHs metabolites for pulmonary health in children and adolescents is limited. Our aim was to examine the effect of single and mixed exposure of urinary PAHs metabolites on lung function among children and adolescents. We included 1417 individuals aged 6–19 years from 3 survey cycles (2007–2008, 2009–2010, 2011–2012) of NHANES program. Multivariable linear regression model was conducted to examine the relationship between urinary PAHs metabolites and lung function index including FEV<sub>1</sub>, FVC and FEV<sub>1</sub>/FVC. BKMR and WQS model were used to evaluate the joint effects of PAHs metabolites for lung function index. Mediation analyses were performed to investigate the mediating role of inflammation related index. Hub proteins were screened by network toxicology and validated using molecular docking. Our results indicated that 3-FLU was negatively linked with FEV<sub>1</sub> and FEV<sub>1</sub>/FVC; 1-OHP was negatively linked with FEV<sub>1</sub>; 1-PYR was negatively linked with FEV<sub>1</sub> and FVC. In addition, 3-OHP was positively corrected with three lung function parameters. In BKMR and WQS models, PAHs metabolites co-exposure was all negatively corrected with FEV<sub>1</sub> and FVC. Systemic inflammation response index mediated the relationship between I-PYR and FEV<sub>1</sub> as well as FVC, with the 8 % and 6 % proportion. IL-6, STAT3, TNF, and TP53 were screened and validated as the common targets related with PAHs, inflammation and lung function by molecular docking analysis. Taken together, our findings raise the concerns about the potential hazards of environmentally relevant PAHs metabolites exposure for respiratory system in the vulnerable population and guide future research into the toxic mechanisms of PAHs metabolites-mediated lung function injury, which has important public health implications.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"292 ","pages":"Article 117990"},"PeriodicalIF":6.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520292","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}
Jinxiao Li , Yanran Wu , Pian Ye , Dongmei Zuo , Shuangjiao Deng , Ran Pang , Huarong Li
{"title":"Computational insights into the inhibitory effects of PFAS 14 on colorectal cancer targeting GSTA1 through competitive binding","authors":"Jinxiao Li , Yanran Wu , Pian Ye , Dongmei Zuo , Shuangjiao Deng , Ran Pang , Huarong Li","doi":"10.1016/j.ecoenv.2025.117925","DOIUrl":"10.1016/j.ecoenv.2025.117925","url":null,"abstract":"<div><div>This study employed computational biology approaches to investigate the interactions between per- and polyfluoroalkyl substances (PFAS) and key colorectal cancer (CRC) proteins. The results indicate that PFAS may influence CRC progression by modulating multiple proteins, particularly glutathione S-transferase A1 (GSTA1). Computational analysis revealed that PFAS 14 exhibits high binding affinity for GSTA1, occupying its glutathione-binding site. Further simulations confirmed the stable binding of PFAS 14 across different environments, forming persistent hydrogen bonds and water bridges, suggesting a potential inhibitory effect on GSTA1.GSTA1, a key member of the glutathione S-transferase family, plays a critical role in detoxification by catalyzing the conjugation of glutathione to electrophilic compounds. Dysregulation of GSTA1 has been implicated in cancer progression and chemoresistance. In CRC, altered GSTA1 expression may affect tumor metabolism and drug response, making it a potential therapeutic target.This study identifies GSTA1 as a key target of PFAS interactions, suggesting that environmental PFAS exposure may influence CRC by interfering with detoxification mechanisms. The competitive inhibition of GSTA1 by PFAS 14 may impact cancer cell survival and progression. Future research should integrate experimental validation to assess its phenotypic effects and evaluate PFAS 14 as a potential GSTA1 inhibitor.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"292 ","pages":"Article 117925"},"PeriodicalIF":6.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529508","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":"Co-application of organic phosphate fertilizer, manure, and biochar synergistically improves chemical and biological properties of Pb-Zn mine tailings: Insights from a pot trial","authors":"Yingru Zhou, Xinlin Xie, Liyu Xia, Meng Wang, Jing Xiang, Taowu Ma","doi":"10.1016/j.ecoenv.2025.117984","DOIUrl":"10.1016/j.ecoenv.2025.117984","url":null,"abstract":"<div><div>The incorporation of amendments is a commonly employed strategy to enhance the effectiveness of phytostabilization in remediating mine tailings. Although the remediation effectiveness of organic phosphate fertilizer (P), manure (M), and biochar (B) as individual amendments for heavy metal pollution has been extensively investigated, yet, the effectiveness of combined amendments for mine tailings remains unknown. The objective of this study is to assess the potential effectiveness of the co-application of P, M, and B in remediating Pb-Zn mine tailings by examining the alterations of chemical and biological properties. In this study, the mine tailings were amended with single and combined P, M, and B at a dosage of 5 % (w/w) followed by a two-month pot trial involving the seeding of ryegrass (<em>Lolium perenne</em> L.). In comparison to the control, all amendments effectively elevated the levels of organic matter, total nitrogen, and total phosphorus in the mine tailings while reducing diethylenetriamine-pentaacetic acid (DTPA)-extractable Pb, Cd, and As; Zn did not show significant changes except in combined treatment with P + M + B (i.e. PMB combination). The combined amendment treatments, particularly PMB, resulted in a substantial enhancement in both microbial biomass and the activities of alkaline phosphatase, urease, invertase, and dehydrogenase. Moreover, the combined amendments facilitated ryegrass growth while concurrently mitigating heavy metal uptake. Pearson's correlation analysis demonstrated a positive association between biological properties of the mine tailings (microbial biomass, enzyme activities, and ryegrass biomass) and nutritional levels while showing a negative correlation with DTPA-extractable heavy metals. Principal component analysis revealed that the addition of PMB exhibited superior efficacy in remediating mine tailings. Overall, our findings suggest that the application of PMB shows promise for <em>in-situ</em> remediation of Pb-Zn mine tailings; however, further research is required to validate these findings under field conditions.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"292 ","pages":"Article 117984"},"PeriodicalIF":6.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512471","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}
Minghao Lv , Wenchong Shi , Jie Xu , Shidong He , Lujun Wang , Mingcong Li , Lanxiang Ma , Jiguang Wang , Fengjie Nie , Bingjie Xu , Yifeng Han , Bo Zhou , Zheng Gao
{"title":"Exposure to thiazole pesticides disrupts pathogens and undermines keystone status of rare taxa within bacterial ecological networks","authors":"Minghao Lv , Wenchong Shi , Jie Xu , Shidong He , Lujun Wang , Mingcong Li , Lanxiang Ma , Jiguang Wang , Fengjie Nie , Bingjie Xu , Yifeng Han , Bo Zhou , Zheng Gao","doi":"10.1016/j.ecoenv.2025.117983","DOIUrl":"10.1016/j.ecoenv.2025.117983","url":null,"abstract":"<div><div>Considering the sensitivity of rare microbial taxa to environmental disturbances and their critical roles in ecosystems, it is essential to investigate how soil microbial communities (particularly rare microbes) respond to pesticide exposure. In this study, we found that thiazole pesticides significantly reduced the severity of potato common scab and effectively disrupted the pathogen’s cell membrane integrity. Notably, hierarchical partitioning analysis indicated that the rare microbial taxa in potato geocaulosphere soil constitute key clusters influencing disease incidence. Within bacterial molecular ecological networks, nodes corresponding to these rare taxa generally exhibited higher degrees compared to those of more abundant taxa. However, pesticide exposure reduced the number of keystone nodes and substantially weakened the hub status of rare bacterial taxa in these networks. These findings suggest that, although thiazole pesticides effectively eradicate pathogens, they may also pose a non-negligible potential risk to rare taxa in agricultural ecosystems.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"292 ","pages":"Article 117983"},"PeriodicalIF":6.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534771","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}
Weilin Zhang , Zhencong Li , Zhongwei Wang , Kuize Liu , Shengbang Huang, Jinguo Liang, Zhiwen Dai, Weixiong Guo, Chao Mao, Siyuan Chen, Jinsong Wei
{"title":"Polyethylene microplastics promote nucleus pulposus cell senescence by inducing oxidative stress via TLR4/NOX2 axis","authors":"Weilin Zhang , Zhencong Li , Zhongwei Wang , Kuize Liu , Shengbang Huang, Jinguo Liang, Zhiwen Dai, Weixiong Guo, Chao Mao, Siyuan Chen, Jinsong Wei","doi":"10.1016/j.ecoenv.2025.117950","DOIUrl":"10.1016/j.ecoenv.2025.117950","url":null,"abstract":"<div><div>This study aimed to detect and characterize microplastics in intervertebral disc and investigate their effects and molecular mechanism on intervertebral disc degeneration. We collected intervertebral disc tissues from cervical, lumbar, and thoracolumbar segments and used Raman spectroscopy to identify and characterize microplastics. Among 80 samples, 47 contained microplastics, with polyethylene being the most prevalent type. To explore the effects of polyethylene microplastics (PE-MPs), we established a mouse model and a nucleus pulposus cell model. Reactive oxygen species (ROS) levels were assessed via immunofluorescence staining, cell viability was measured using the CCK-8 assay, and protein expression related to the Toll-like receptor 4 (TLR4)/NADPH oxidase 2 (NOX2) axis, oxidative stress, and nucleus pulposus degeneration were evaluated through western blotting and immunofluorescence staining. Results showed that PE-MPs exposure led to intervertebral disc degeneration by inducing oxidative stress and activating the TLR4 / NOX2 axis, which increased the senescence of nucleus pulposus cells. These effects were mitigated by TLR4 and NOX2 inhibitors. This research highlights the existence of microplastics in human intervertebral disc tissue and unveils a novel mechanism of nucleus pulposus cell senescence induced by PE-MPs, offering new avenues for clinical treatment of microplastic-related disc degeneration.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"292 ","pages":"Article 117950"},"PeriodicalIF":6.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512468","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}
Yi Wang, Xuling Su, Qianqian Wang, Likun Zhang, Yaling Yu, Yiwei Zhao, Zhiyan Liu
{"title":"Bisphenol A exposure enhances proliferation and tumorigenesis of papillary thyroid carcinoma through ROS generation and activation of NOX4 signaling pathways","authors":"Yi Wang, Xuling Su, Qianqian Wang, Likun Zhang, Yaling Yu, Yiwei Zhao, Zhiyan Liu","doi":"10.1016/j.ecoenv.2025.117946","DOIUrl":"10.1016/j.ecoenv.2025.117946","url":null,"abstract":"<div><div>As a prevalent industrial material and component of consumer products, bisphenol A (BPA) is linked to hormone homeostasis disruption and potential carcinogenicity. However, the precise mechanisms through which BPA contributes to thyroid carcinogenesis, especially in papillary thyroid carcinoma (PTC), are not fully understood. This study investigates how BPA boosts the proliferation and tumorigenic characteristics of thyroid cells. BPA exposure significantly increased cell proliferation in a duration-dependent manner at a concentration of 0.5 μM, which is slightly higher than human exposure levels. Therefore, this study utilized BPA treatment concentrations of 0.1 µM and 0.5 µM. BPA augmented the invasiveness of PTC cells with a dependency on both dosage and temporal factors. RNA-seq and gene expression analysis from normal human thyroid follicular epithelial cells suggested that BPA upregulated genes related to oxidative stress and thyroid cancer. Concurrently, our study revealed significant upregulation of NOX4 in thyroid tumors compared to normal thyroid tissues, with higher expression levels observed in advanced carcinomas by analyses of the TCGA database. BPA induces the upregulation of NOX4 in human thyroid cells, thereby triggering the activation of MAPK and PI3K/AKT pathways. In xenograft models, BPA treatment resulted in increased tumor size and Ki-67 proliferation index, accompanied by upregulated NOX4 expression. Additionally, BPA exposure led to higher levels of free triiodothyronine (FT<sub>3</sub>), indicating thyroid hormone disruption. Mechanistically, BPA activates the MAPK and PI3K/AKT pathways via NOX4, leading to increased ROS production and cell proliferation. This was further demonstrated through the use of ROS scavenger treatment and si-NOX4, which showed that BPA stimulates ROS generation by activating NOX4/MAPK and NOX4/PI3K/AKT pathways in thyroid cells. This finding enhances our understanding of the pathogenesis of PTC related to BPA exposure and highlights the necessity for rigorous health risk assessments regarding BPA exposure.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"292 ","pages":"Article 117946"},"PeriodicalIF":6.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508911","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}
Ningning Yang , Kemin Jia , Kaixi Dai , Qifang Wu , Huanjuan Yan , Haibin Tong , Ya Zhang , Xia Shao
{"title":"Perfluorooctane sulfonate mediates GSH degradation leading to oral keratinocytes ferroptosis and mucositis through activation of the ER stress-ATF4-CHAC1 axis","authors":"Ningning Yang , Kemin Jia , Kaixi Dai , Qifang Wu , Huanjuan Yan , Haibin Tong , Ya Zhang , Xia Shao","doi":"10.1016/j.ecoenv.2025.117964","DOIUrl":"10.1016/j.ecoenv.2025.117964","url":null,"abstract":"<div><div>Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that induces inflammatory response and oxidative stress in oral mucosa. Ferroptosis, a form of cell death characterized by iron-dependent lipid peroxidation (the oxidative degradation of lipids), was believed to play a crucial role in pathogenesis of oral mucositis; however, the involvement of PFOS-induced ferroptosis remained unclear. Our findings demonstrated that PFOS inhibited proliferation and induced pro-apoptotic effects in oral cells, with the most pronounced effects observed in human oral keratinocytes (HOK). PFOS significantly increased reactive oxygen species (ROS) and lipid peroxidation, and depleted glutathione (GSH) in HOK cells. Notably, PFOS decreased glutathione peroxidase 4 (GPX4) expression and elevated Fe<sup>2 +</sup> levels, suggesting a potential induction of ferroptosis. Ferroptosis inhibitors mitigated PFOS-induced lipid peroxidation and GSH depletion, subsequently enhancing cell viability. Mechanistically, PFOS-induced endoplasmic reticulum (ER) stress contributed to the increased expression and nuclear translocation (from the cytoplasm into the nucleus) of activating transcription factor 4 (ATF4) and up-regulated its downstream target gene <em>Chac1</em>. Glutathione-specific gamma-glutamylcyclotransferase 1 (CHAC1) catalyzed the conversion of GSH into cysteinylglycine and 5-oxoproline, resulting in GSH depletion—a critical factor in PFOS-induced ferroptosis. Knocking down CHAC1 attenuated PFOS-induced ferroptosis. Tauroursodeoxycholic acid (TUDCA), the classical ER stress inhibitor, attenuated PFOS-induced oral keratinocytes ferroptosis and mucositis by inhibiting ATF4/CHAC1 pathway activation. These findings elucidated the toxicological mechanisms of PFOS and proposed potential therapeutic strategies to counteract PFOS exposure induced oral mucositis.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"292 ","pages":"Article 117964"},"PeriodicalIF":6.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529597","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}