Pub Date : 2025-12-01Epub Date: 2025-11-26DOI: 10.1016/j.etap.2025.104879
Chloé ML. Argoul , Pierre-Louis Toutain , Sarah Berard , Nicole Picard-Hagen , Véronique Gayrard , Marlène Z. Lacroix
Understanding interspecies and structure-based differences in the toxicokinetics of perfluoroalkyl substances (PFAS) is important to explain their persistence and improve health risk assessment. Since renal clearance is the main elimination pathway, this study measured the free (protein-unbound) fraction (fu) of PFAS in human and mouse plasma using the DianormR system, selected for its robustness and rapid equilibrium. Sixteen PFAS were tested, including perfluoroalkyl carboxylic acids (PFCA), sulfonic acids (PFSA), and ether derivatives (PFECA). Mean fu values ranged from 0.21 % (PFOS) to 50 % (PFPeA) in mice and from 0.02 % (PFHpS) to 8.5 % (PFPeA) in humans. Interspecies differences were most pronounced for short-chain PFAS and PFECA, but not observed for longer chains. A U-shaped relationship between fu and molecular weight (MW) was found, with the lowest values near 400–500 g/mol. These results highlight plasma protein binding as a key determinant of PFAS persistence and provide predictive models linking fu to MW.
{"title":"Structure-related differences in plasma protein binding of per- and polyfluoroalkyl substances in mice and humans","authors":"Chloé ML. Argoul , Pierre-Louis Toutain , Sarah Berard , Nicole Picard-Hagen , Véronique Gayrard , Marlène Z. Lacroix","doi":"10.1016/j.etap.2025.104879","DOIUrl":"10.1016/j.etap.2025.104879","url":null,"abstract":"<div><div>Understanding interspecies and structure-based differences in the toxicokinetics of perfluoroalkyl substances (PFAS) is important to explain their persistence and improve health risk assessment. Since renal clearance is the main elimination pathway, this study measured the free (protein-unbound) fraction (f<sub>u</sub>) of PFAS in human and mouse plasma using the Dianorm<sup>R</sup> system, selected for its robustness and rapid equilibrium. Sixteen PFAS were tested, including perfluoroalkyl carboxylic acids (PFCA), sulfonic acids (PFSA), and ether derivatives (PFECA). Mean f<sub>u</sub> values ranged from 0.21 % (PFOS) to 50 % (PFPeA) in mice and from 0.02 % (PFHpS) to 8.5 % (PFPeA) in humans. Interspecies differences were most pronounced for short-chain PFAS and PFECA, but not observed for longer chains. A U-shaped relationship between f<sub>u</sub> and molecular weight (MW) was found, with the lowest values near 400–500 g/mol. These results highlight plasma protein binding as a key determinant of PFAS persistence and provide predictive models linking f<sub>u</sub> to MW.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104879"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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}
Pub Date : 2025-12-01Epub Date: 2025-11-07DOI: 10.1016/j.etap.2025.104863
Stefano Magni , Andrea Binelli , Lara Nigro , Eva Roubeau Dumont , Emmanuel Eysseric , Riccardo Sbarberi , Luca Del Giacco , Alberto Diana , Camilla Della Torre , Christian Gagnon , François Gagné
This study focuses on the sub-lethal effects of three key tire rubber-derived contaminants (TRDCs) used as vulcanizing agents and antioxidants in the tire production: 1,3-diphenylguanidine (DPG), N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD), and its byproduct 6PPD-quinone (6PPD-q). Effects were assessed at the concentration of 500 ng/L on Danio rerio (zebrafish) larvae, from 0 to 120 h post fertilization, through a wide battery of biomarkers, proteomics, as well as imaging techniques for the inflammation detection. No significant effects were observed on larvae concerning apical endpoints, such as viability and morphological alterations, in all experimental groups. However, DPG exposure led to the most widespread biomarker responses among the tested compounds, with a significant induction of superoxide dismutase, ethoxyresorufin-O-deethylase and glutathione-S-transferase. To obtain a toxicity scale of tested TRDCs, based on used biomarkers, each endpoint was integrated in the Biomarker Response Index. This approach indicated that 6PPD-q and DPG were more toxic than 6PPD. Coherently, proteomic analysis revealed the modulation of 8 proteins with the DPG treatment, 7 with 6PPD-q and only 4 impacted proteins in the treatment with 6PPD. Other evidence, which considers also the effects of TRDC mixture, is necessary to better investigate the main toxic chemicals related to tire in aquatic ecosystems.
本研究重点研究了轮胎生产中作为硫化剂和抗氧化剂的三种关键轮胎橡胶衍生污染物（trdc）： 1,3-二苯基胍（DPG）、N-（1,3-二甲基丁基）-N ' -苯基-对苯二胺（6PPD）及其副产物6PPD-醌（6PPD-q）的亚致死效应。通过广泛的生物标志物、蛋白质组学和炎症检测成像技术，评估了500 ng/L浓度对斑马鱼（Danio rerio）幼虫在受精后0至120 h的影响。在所有实验组中，对幼虫的生存力和形态变化等尖端端点均无显著影响。然而，DPG暴露导致了测试化合物中最广泛的生物标志物反应，显著诱导了超氧化物歧化酶、乙氧基间苯二酚- o -去乙基化酶和谷胱甘肽- s -转移酶。为了获得测试trdc的毒性等级，基于使用的生物标志物，将每个终点整合到生物标志物反应指数中。该方法表明6PPD-q和DPG的毒性大于6PPD。蛋白质组学分析一致显示，DPG处理可调节8个蛋白，6PPD-q处理可调节7个蛋白，6PPD处理仅影响4个蛋白。为了更好地调查水生生态系统中与轮胎有关的主要有毒化学物质，有必要提供其他证据，这些证据也考虑了TRDC混合物的影响。
{"title":"Assessment of the sub-lethal effects induced by three tire rubber-derived contaminants on zebrafish larvae","authors":"Stefano Magni , Andrea Binelli , Lara Nigro , Eva Roubeau Dumont , Emmanuel Eysseric , Riccardo Sbarberi , Luca Del Giacco , Alberto Diana , Camilla Della Torre , Christian Gagnon , François Gagné","doi":"10.1016/j.etap.2025.104863","DOIUrl":"10.1016/j.etap.2025.104863","url":null,"abstract":"<div><div>This study focuses on the sub-lethal effects of three key tire rubber-derived contaminants (TRDCs) used as vulcanizing agents and antioxidants in the tire production: 1,3-diphenylguanidine (DPG), N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD), and its byproduct 6PPD-quinone (6PPD-q). Effects were assessed at the concentration of 500 ng/L on <em>Danio rerio</em> (zebrafish) larvae, from 0 to 120 h post fertilization, through a wide battery of biomarkers, proteomics, as well as imaging techniques for the inflammation detection<em>.</em> No significant effects were observed on larvae concerning apical endpoints, such as viability and morphological alterations, in all experimental groups. However, DPG exposure led to the most widespread biomarker responses among the tested compounds, with a significant induction of superoxide dismutase, ethoxyresorufin-O-deethylase and glutathione-S-transferase. To obtain a toxicity scale of tested TRDCs, based on used biomarkers, each endpoint was integrated in the Biomarker Response Index. This approach indicated that 6PPD-q and DPG were more toxic than 6PPD. Coherently, proteomic analysis revealed the modulation of 8 proteins with the DPG treatment, 7 with 6PPD-q and only 4 impacted proteins in the treatment with 6PPD. Other evidence, which considers also the effects of TRDC mixture, is necessary to better investigate the main toxic chemicals related to tire in aquatic ecosystems.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104863"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145461653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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}
Pub Date : 2025-12-01Epub Date: 2025-11-12DOI: 10.1016/j.etap.2025.104865
Martina Poncarová , Michal Šorf , Pavla Fojtíková , Šárka Klementová , Eva Poštulková , Karel Hořejší , Veronika Oušková , Monika Křížová , Martin Hána
Photochemical degradation of the antidiabetic drug metformin in the presence of a quinone sensitiser was investigated under environmentally relevant UV light. Degradation products were identified using UHPLC-Q-TOF. The effects of the resulting photoproduct mixture and metformin itself (50–100 µg l⁻¹) were assessed on four aquatic species representing different trophic levels: Desmodesmus subspicatus, Lemna minor, Daphnia magna and Danio rerio embryos. The photoproduct mixture caused growth inhibition in photosynthesising organisms, reproductive disruption in Daphnia, developmental malformations in fish embryos, and significant changes in oxidative stress markers. This study provides the first evidence that photochemically generated transformation products of metformin are significantly more toxic than the parent compound, even at environmentally relevant concentrations. These findings highlight the importance of including not only parent pharmaceuticals but also their photoproducts in environmental risk assessments, as the latter may pose a greater ecological hazard in surface waters.
研究了抗糖尿病药物二甲双胍在醌类致敏剂存在下在环境相关紫外光下的光化学降解。用UHPLC-Q-TOF对降解产物进行鉴定。所产生的光产物混合物和二甲双胍本身（50-100 µg l - 1）对代表不同营养水平的四种水生物种的影响进行了评估：亚spicatus Desmodesmus， lena minor， Daphnia magna和Danio rerio胚胎。光产物混合物导致光合生物生长抑制，水蚤繁殖中断，鱼类胚胎发育畸形，氧化应激标志物发生显著变化。这项研究首次证明，即使在与环境相关的浓度下，光化学生成的二甲双胍转化产物的毒性也明显高于母体化合物。这些发现强调了在环境风险评估中不仅包括母体药物，而且包括其光产物的重要性，因为后者可能在地表水中造成更大的生态危害。
{"title":"Identification of the photoproducts of the antidiabetic drug metformin and the different impact of metformin compared to its photoproducts mixture on aquatic organisms","authors":"Martina Poncarová , Michal Šorf , Pavla Fojtíková , Šárka Klementová , Eva Poštulková , Karel Hořejší , Veronika Oušková , Monika Křížová , Martin Hána","doi":"10.1016/j.etap.2025.104865","DOIUrl":"10.1016/j.etap.2025.104865","url":null,"abstract":"<div><div>Photochemical degradation of the antidiabetic drug metformin in the presence of a quinone sensitiser was investigated under environmentally relevant UV light. Degradation products were identified using UHPLC-Q-TOF. The effects of the resulting photoproduct mixture and metformin itself (50–100 µg l⁻¹) were assessed on four aquatic species representing different trophic levels: <em>Desmodesmus subspicatus</em>, <em>Lemna minor</em>, <em>Daphnia magna</em> and <em>Danio rerio</em> embryos. The photoproduct mixture caused growth inhibition in photosynthesising organisms, reproductive disruption in <em>Daphnia</em>, developmental malformations in fish embryos, and significant changes in oxidative stress markers. This study provides the first evidence that photochemically generated transformation products of metformin are significantly more toxic than the parent compound, even at environmentally relevant concentrations. These findings highlight the importance of including not only parent pharmaceuticals but also their photoproducts in environmental risk assessments, as the latter may pose a greater ecological hazard in surface waters.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104865"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145515640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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}
Pub Date : 2025-12-01Epub Date: 2025-11-19DOI: 10.1016/j.etap.2025.104873
Aml M. Abo Al-Saoud , Mohammed Nagib A. Hasaneen , Ali Noory Fajer , Ibrahim S. Kamel
Solid lipid nanoparticles (SLNPs) are emerging as promising nanocarriers for various therapeutic agents being used in medicine or agriculture. However, understanding their toxic effects is crucial for their safe application in drug delivery systems. Therefore, this study aimed to evaluate the phytotoxic and cyto-genotoxic effects of SLNPs. SLNPs were synthesized at a concentration of 5 g/100 ml, coded as R and diluted for testing its toxicity using Vicia faba as a bioindicator. V. faba seedlings were exposed to five concentrations of SLNPs (R:5 g/100 ml; 0.5 R: 2.5 g/100 ml, 0.25 R: 1.25 g/100 ml, 0.125 R: 0.63 g/100 ml and 0.0625 R: 0.31 g/100 ml) and control (distilled water). Parameters such as root growth and histology, catalase enzyme activity, mitotic index, chromosomal anomalies and apoptosis percentages besides cell cycle progression were assessed. Results discovered a concentration-dependent increase in phototoxic effect revealed by significant inhibition percentages in root length (15.08 %–45.25 %) at high levels of SLNPs (0.5 R: 2.5 g/100 ml and R: 5 g/100 ml). Moreover, histological observation indicated that concentrations above the dilution of 0.125 R of SLNPs induces various histological alterations as reduced root diameter and filling the metaxylem with parenchyma cells which might impair the uptake and transport of solutes adversely affect plant health and life. Theses alterations might adopt the significant increases in catalase enzyme activity in root tissue in dose-dependent manner. Significant mitotic index and cell viability reduction and alterations in cell cycle distribution especially the obvious DNA synthesis phase arrest at the concentration of 5 g/100 ml and increased frequency of chromosomal anomalies suggesting SLNPs cyto-genotoxicity. These findings concluded that SLNPs of 5 g/100 ml is toxic can have adverse effects on V. faba plant health. Further studies needed in this regard.
{"title":"A novel in vivo toxicity profiling of solid lipid nanoparticles (SLNPs) in Vicia faba seedlings as a plant model","authors":"Aml M. Abo Al-Saoud , Mohammed Nagib A. Hasaneen , Ali Noory Fajer , Ibrahim S. Kamel","doi":"10.1016/j.etap.2025.104873","DOIUrl":"10.1016/j.etap.2025.104873","url":null,"abstract":"<div><div>Solid lipid nanoparticles (SLNPs) are emerging as promising nanocarriers for various therapeutic agents being used in medicine or agriculture. However, understanding their toxic effects is crucial for their safe application in drug delivery systems. Therefore, this study aimed to evaluate the phytotoxic and cyto-genotoxic effects of SLNPs. SLNPs were synthesized at a concentration of 5 g/100 ml, coded as R and diluted for testing its toxicity using <em>Vicia faba</em> as a bioindicator. <em>V. faba</em> seedlings were exposed to five concentrations of SLNPs (R:5 g/100 ml; 0.5 R: 2.5 g/100 ml, 0.25 R: 1.25 g/100 ml, 0.125 R: 0.63 g/100 ml and 0.0625 R: 0.31 g/100 ml) and control (distilled water). Parameters such as root growth and histology, catalase enzyme activity, mitotic index, chromosomal anomalies and apoptosis percentages besides cell cycle progression were assessed. Results discovered a concentration-dependent increase in phototoxic effect revealed by significant inhibition percentages in root length (15.08 %–45.25 %) at high levels of SLNPs (0.5 R: 2.5 g/100 ml and R: 5 g/100 ml). Moreover, histological observation indicated that concentrations above the dilution of 0.125 R of SLNPs induces various histological alterations as reduced root diameter and filling the metaxylem with parenchyma cells which might impair the uptake and transport of solutes adversely affect plant health and life. Theses alterations might adopt the significant increases in catalase enzyme activity in root tissue in dose-dependent manner. Significant mitotic index and cell viability reduction and alterations in cell cycle distribution especially the obvious DNA synthesis phase arrest at the concentration of 5 g/100 ml and increased frequency of chromosomal anomalies suggesting SLNPs cyto-genotoxicity. These findings concluded that SLNPs of 5 g/100 ml is toxic can have adverse effects on <em>V. faba</em> plant health. Further studies needed in this regard.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104873"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145575065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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}
Pub Date : 2025-12-01Epub Date: 2025-10-20DOI: 10.1016/j.etap.2025.104850
Manel M. Habel , Adrian C. Williams , Vitaliy V. Khutoryanskiy
The principle of the 3Rs—Reduction, Refinement, and Replacement—encourages minimizing animal use, improving experimental design, and developing alternative models for toxicology testing. Among such models, planaria (aquatic flatworms) have gained increasing attention in pharmacology, regenerative medicine, and toxicology because of their simple anatomy, high environmental sensitivity, exceptional regenerative ability, and ease of laboratory maintenance. In this study, we examined the effects of benzalkonium chloride (BAC)—a commonly used pharmaceutical excipient with antimicrobial and permeability-enhancing properties, as well as a known environmental toxicant—on the locomotor activity of Schmidtea mediterranea using both manual assessment and Lolitrack video-tracking software. Six concentrations of BAC (5–1000 μg/mL) and a negative control were tested. Both approaches showed an overall reduction in locomotor activity over time, though manual analysis indicated a transient stimulation at lower concentrations. The software-based method demonstrated greater reliability, precision, and objectivity, making it preferable for toxicity evaluation in planaria.
{"title":"Toxicological assessment of benzalkonium chloride using planaria mobility: A comparison of manual and digital tracking methods","authors":"Manel M. Habel , Adrian C. Williams , Vitaliy V. Khutoryanskiy","doi":"10.1016/j.etap.2025.104850","DOIUrl":"10.1016/j.etap.2025.104850","url":null,"abstract":"<div><div>The principle of the 3Rs—Reduction, Refinement, and Replacement—encourages minimizing animal use, improving experimental design, and developing alternative models for toxicology testing. Among such models, planaria (aquatic flatworms) have gained increasing attention in pharmacology, regenerative medicine, and toxicology because of their simple anatomy, high environmental sensitivity, exceptional regenerative ability, and ease of laboratory maintenance. In this study, we examined the effects of benzalkonium chloride (BAC)—a commonly used pharmaceutical excipient with antimicrobial and permeability-enhancing properties, as well as a known environmental toxicant—on the locomotor activity of <em>Schmidtea mediterranea</em> using both manual assessment and Lolitrack video-tracking software. Six concentrations of BAC (5–1000 μg/mL) and a negative control were tested. Both approaches showed an overall reduction in locomotor activity over time, though manual analysis indicated a transient stimulation at lower concentrations. The software-based method demonstrated greater reliability, precision, and objectivity, making it preferable for toxicity evaluation in planaria.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104850"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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}
Pub Date : 2025-12-01Epub Date: 2025-11-12DOI: 10.1016/j.etap.2025.104868
Raquel Maroto Cejudo , Denisse Michelle Espinosa Encalada , María Granada Picazo Martínez , Mónica Gómez-Juarez Sango , Fernando Andrés-Pretel , Carlos Cava Valenciano
Introduction
Sevoflurane (SF) has been reported to exhibit topical analgesic/antimicrobial effects. This study evaluated its cytotoxicity on the ocular surface by comparing SF with povidone-iodine (PI) and balanced saline solution (BSS) in an epithelial cell model.
Methods
Cytotoxicity was assessed using the Short-Time Exposure Test (OECD 491) on Seruminstitut Rabbit Cornea (SIRC) cells. Cultures were exposed for 5 min to SF (100 %), PI (5 %) or BSS and viability was determined by the MTT assay. Recovery at 0, 30, and 60 min and the effect of a double SF exposure were also evaluated.
Results
Median viabilities were: 85.3 % for SF, 0.5 % for PI and 97.3 % for BSS (p = 0.005). Significant differences were found between 0 and 30 min (p = 0.021) and 0–60 min (p = 0.038). Double exposure did not significantly modify SF viability (p > 0.05).
Conclusions
SF did not demonstrate significant cytotoxicity in vitro, unlike PI. However, in vivo studies are required to confirm its ocular safety.
{"title":"Evaluation of the ocular cytotoxicity of topical sevoflurane in sirc cells: An in vitro study","authors":"Raquel Maroto Cejudo , Denisse Michelle Espinosa Encalada , María Granada Picazo Martínez , Mónica Gómez-Juarez Sango , Fernando Andrés-Pretel , Carlos Cava Valenciano","doi":"10.1016/j.etap.2025.104868","DOIUrl":"10.1016/j.etap.2025.104868","url":null,"abstract":"<div><h3>Introduction</h3><div>Sevoflurane (SF) has been reported to exhibit topical analgesic/antimicrobial effects. This study evaluated its cytotoxicity on the ocular surface by comparing SF with povidone-iodine (PI) and balanced saline solution (BSS) in an epithelial cell model.</div></div><div><h3>Methods</h3><div>Cytotoxicity was assessed using the Short-Time Exposure Test (OECD 491) on Seruminstitut Rabbit Cornea (SIRC) cells. Cultures were exposed for 5 min to SF (100 %), PI (5 %) or BSS and viability was determined by the MTT assay. Recovery at 0, 30, and 60 min and the effect of a double SF exposure were also evaluated.</div></div><div><h3>Results</h3><div>Median viabilities were: 85.3 % for SF, 0.5 % for PI and 97.3 % for BSS (p = 0.005). Significant differences were found between 0 and 30 min (p = 0.021) and 0–60 min (p = 0.038). Double exposure did not significantly modify SF viability (p > 0.05).</div></div><div><h3>Conclusions</h3><div>SF did not demonstrate significant cytotoxicity in vitro, unlike PI. However, in vivo studies are required to confirm its ocular safety.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104868"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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}
Pub Date : 2025-12-01Epub Date: 2025-11-08DOI: 10.1016/j.etap.2025.104864
Sofia Neves , Solange A. Pacheco , Fátima Vaz , Cristina Valentim-Coelho , Joana Saraiva , Peter James , Tânia Simões , Deborah Penque
Chronic exposure to second-hand smoke (SHS) contributes to the development of health issues, including cancer and cardiovascular diseases. Molecular mechanisms underlying SHS-related diseases remain poorly understood, highlighting the need for reliable risk assessment biomarkers. Herein, we demonstrate that the plasma proteome of individuals exposed to SHS undergoes significant modulation. Butyrylcholinesterase (BChE) and Vitamin D-binding protein (GC) that are involved in the physiological response to circulating toxic substances, as well as key mediators of systemic inflammation, including Complement C1r subcomponent (C1R), Complement C1q subcomponent subunit C (C1QC), Histidine-rich glycoprotein (HRG), and Vitamin K-dependent protein S (PROS1), were found to be significantly modulated in SHS-exposed individuals. Moreover, strong indicators of a pro-atherothrombotic response such Apolipoprotein A-IV (APOA4) and Alpha-2-antiplasmin (SERPINF2), were also differentially expressed. These findings provide novel insights into the biological pathways linking SHS-exposure to cardiovascular risks, and suggest a panel of candidate proteins with potential utility as SHS-risk assessment biomarkers.
长期接触二手烟会导致健康问题的发展，包括癌症和心血管疾病。shs相关疾病的分子机制尚不清楚，因此需要可靠的风险评估生物标志物。在此，我们证明了暴露于SHS的个体的血浆蛋白质组经历了显著的调节。研究发现，参与循环有毒物质生理反应的丁基胆碱酯酶（BChE）和维生素d结合蛋白（GC），以及全身性炎症的关键介质，包括补体C1r亚组分（C1r）、补体C1q亚组分亚基C （C1QC）、富组氨酸糖蛋白（HRG）和维生素k依赖性蛋白S (PROS1)，在shs暴露个体中被显著调节。此外，促动脉粥样硬化血栓反应的强指标，如载脂蛋白a- iv （APOA4）和α -2抗纤溶蛋白（serinf2），也有差异表达。这些发现为将shs暴露与心血管风险联系起来的生物学途径提供了新的见解，并提出了一组具有潜在效用的候选蛋白作为shs风险评估生物标志物。
{"title":"Second-hand smoke exposure modulates plasma proteins linked to detoxification, inflammation and atherothrombosis","authors":"Sofia Neves , Solange A. Pacheco , Fátima Vaz , Cristina Valentim-Coelho , Joana Saraiva , Peter James , Tânia Simões , Deborah Penque","doi":"10.1016/j.etap.2025.104864","DOIUrl":"10.1016/j.etap.2025.104864","url":null,"abstract":"<div><div>Chronic exposure to second-hand smoke (SHS) contributes to the development of health issues, including cancer and cardiovascular diseases. Molecular mechanisms underlying SHS-related diseases remain poorly understood, highlighting the need for reliable risk assessment biomarkers. Herein, we demonstrate that the plasma proteome of individuals exposed to SHS undergoes significant modulation. Butyrylcholinesterase (BChE) and Vitamin <span>D</span>-binding protein (GC) that are involved in the physiological response to circulating toxic substances, as well as key mediators of systemic inflammation, including Complement C1r subcomponent (C1R), Complement C1q subcomponent subunit C (C1QC), Histidine-rich glycoprotein (HRG), and Vitamin K-dependent protein S (PROS1), were found to be significantly modulated in SHS-exposed individuals. Moreover, strong indicators of a pro-atherothrombotic response such Apolipoprotein A-IV (APOA4) and Alpha-2-antiplasmin (SERPINF2), were also differentially expressed. These findings provide novel insights into the biological pathways linking SHS-exposure to cardiovascular risks, and suggest a panel of candidate proteins with potential utility as SHS-risk assessment biomarkers.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104864"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145461652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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}
Silver nanoparticles (AgNPs) are widely used for their antimicrobial properties, yet their neurotoxic mechanisms remain under-explored. Ferroptosis, an iron-dependent regulated cell-death pathway implicated in neurological disorders, has not been fully considered in AgNPs-induced neuronal injury. Here, exposures of HT22 mouse hippocampal neurons to AgNPs (2–8 µg/mL) or AgNO3 (0.15–0.6 µg/mL) reduce viability, disrupt iron homeostasis, trigger lipid peroxidation, downregulate GPX4 and upregulate SLC7A11 (system Xc⁻/GPX4 axis), and alter ferroptosis-related proteins (TFRC, FTH1, FTL, ACSL4, COX2). Ferroptosis inhibitors (deferoxamine, Ferrostatin-1) mitigate these effects. Notably, although AgNO3 induced greater Ag+ uptake, AgNPs produced equivalent ferroptotic responses, suggesting nanoparticle-specific mechanisms beyond ionic release. These findings echo our previous in vivo data showing that AgNPs exposure impairs learning and memory in mice. Collectively, our results indicate that AgNPs provoke ferroptosis in hippocampal neurons via iron-dysregulation and antioxidant failure, and our inhibitor-based in vitro study offers mechanistic insight that may guide future therapeutic strategies.
{"title":"Silver nanoparticles induce ferroptosis via iron dyshomeostasis and system Xc⁻/GPX4 axis dysregulation in HT22 cells","authors":"Shuyan Niu, Menghao Guo, Haitao Yang, Xiaoru Chang, Mengting Shang, Chenyu Liu, Mengjing Cui, Tianshu Wu, Yuying Xue","doi":"10.1016/j.etap.2025.104856","DOIUrl":"10.1016/j.etap.2025.104856","url":null,"abstract":"<div><div>Silver nanoparticles (AgNPs) are widely used for their antimicrobial properties, yet their neurotoxic mechanisms remain under-explored. Ferroptosis, an iron-dependent regulated cell-death pathway implicated in neurological disorders, has not been fully considered in AgNPs-induced neuronal injury. Here, exposures of HT22 mouse hippocampal neurons to AgNPs (2–8 µg/mL) or AgNO<sub>3</sub> (0.15–0.6 µg/mL) reduce viability, disrupt iron homeostasis, trigger lipid peroxidation, downregulate GPX4 and upregulate SLC7A11 (system Xc⁻/GPX4 axis), and alter ferroptosis-related proteins (TFRC, FTH1, FTL, ACSL4, COX2). Ferroptosis inhibitors (deferoxamine, Ferrostatin-1) mitigate these effects. Notably, although AgNO<sub>3</sub> induced greater Ag<sup>+</sup> uptake, AgNPs produced equivalent ferroptotic responses, suggesting nanoparticle-specific mechanisms beyond ionic release. These findings echo our previous <em>in vivo</em> data showing that AgNPs exposure impairs learning and memory in mice. Collectively, our results indicate that AgNPs provoke ferroptosis in hippocampal neurons via iron-dysregulation and antioxidant failure, and our inhibitor-based <em>in vitro</em> study offers mechanistic insight that may guide future therapeutic strategies.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104856"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145383662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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}
Pub Date : 2025-12-01Epub Date: 2025-11-26DOI: 10.1016/j.etap.2025.104880
Akshita Verma, Samuel Sunday Ogunsola, Kaylyn A. Keith, G.D. Thouli L. Jayawardana
Illicit drugs and novel psychoactive substances (NPS) in aquatic environments pose growing ecological and public health concerns due to their persistence and toxicity. Released mainly via wastewater and runoff, their transport and fate are influenced by microbial degradation, hydrology, and bioaccumulation. These compounds have been detected in freshwater and marine ecosystems, causing endocrine disruption and toxicity in aquatic organisms, with potential human exposure through water and food. Advances in high-resolution mass spectrometry (HRMS) have improved their detection, while treatment technologies such as advanced oxidation, membrane filtration, and bioremediation are being developed to remove these residues. This review integrates findings from environmental chemistry, ecotoxicology, and public health to assess the sources, behavior, impacts, and mitigation of illicit drugs and NPS in aquatic systems. It highlights the complexity of these contaminants and identifies critical knowledge gaps that must be addressed to support effective monitoring, risk assessment, and regulatory strategies.
{"title":"Environmental fate of illicit drugs and new psychoactive substances in aquatic systems: Impact, critical insights, and future directions","authors":"Akshita Verma, Samuel Sunday Ogunsola, Kaylyn A. Keith, G.D. Thouli L. Jayawardana","doi":"10.1016/j.etap.2025.104880","DOIUrl":"10.1016/j.etap.2025.104880","url":null,"abstract":"<div><div>Illicit drugs and novel psychoactive substances (NPS) in aquatic environments pose growing ecological and public health concerns due to their persistence and toxicity. Released mainly via wastewater and runoff, their transport and fate are influenced by microbial degradation, hydrology, and bioaccumulation. These compounds have been detected in freshwater and marine ecosystems, causing endocrine disruption and toxicity in aquatic organisms, with potential human exposure through water and food. Advances in high-resolution mass spectrometry (HRMS) have improved their detection, while treatment technologies such as advanced oxidation, membrane filtration, and bioremediation are being developed to remove these residues. This review integrates findings from environmental chemistry, ecotoxicology, and public health to assess the sources, behavior, impacts, and mitigation of illicit drugs and NPS in aquatic systems. It highlights the complexity of these contaminants and identifies critical knowledge gaps that must be addressed to support effective monitoring, risk assessment, and regulatory strategies.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104880"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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}
Pub Date : 2025-12-01Epub Date: 2025-11-19DOI: 10.1016/j.etap.2025.104874
Ruiz-Sobremazas Diego , Coca Mario , Morales-Navas Miguel , Nerea Rios Nieto , Rodulfo-Cárdenas Rocío , Colomina Maria Teresa , López-Granero Caridad , Sanchez-Santed Fernando , Perez-Fernandez Cristian
Environmental exposure to air pollution, specially to particulate matter (PM) during pregnancy, plays a significant role in increasing the risk of neurodevelopmental disorders such as autism. This study investigated the long-term impact of oral gestational PM exposure (200 µg/kg/day) on memory in aged rats using the Morris Water Maze (MWM). After completing MWM, hippocampal tissue was collected and analyzed for gene expression. Our findings indicate that gestational PM exposure caused no major developmental alterations, aside from slightly poorer performance in the adherence test. No differences were detected in standard MWM manipulations, however, PM-offspring showed reduced latency in the test session, suggesting a possible compulsive-like behavior. Additionally, hippocampal gene expression revealed downregulation of several genes, including NMDA and GABAergic subunits. These effects depended on exposure and sex. The behavioral effects might reflect cognitive inflexibility linked to gene alterations. Further research is needed to clarify these outcomes.
{"title":"Long-term impact of oral gestational PM10 exposure on morris water maze performance and hippocampal gene expression","authors":"Ruiz-Sobremazas Diego , Coca Mario , Morales-Navas Miguel , Nerea Rios Nieto , Rodulfo-Cárdenas Rocío , Colomina Maria Teresa , López-Granero Caridad , Sanchez-Santed Fernando , Perez-Fernandez Cristian","doi":"10.1016/j.etap.2025.104874","DOIUrl":"10.1016/j.etap.2025.104874","url":null,"abstract":"<div><div>Environmental exposure to air pollution, specially to particulate matter (PM) during pregnancy, plays a significant role in increasing the risk of neurodevelopmental disorders such as autism. This study investigated the long-term impact of oral gestational PM exposure (200 µg/kg/day) on memory in aged rats using the Morris Water Maze (MWM). After completing MWM, hippocampal tissue was collected and analyzed for gene expression. Our findings indicate that gestational PM exposure caused no major developmental alterations, aside from slightly poorer performance in the adherence test. No differences were detected in standard MWM manipulations, however, PM-offspring showed reduced latency in the test session, suggesting a possible compulsive-like behavior. Additionally, hippocampal gene expression revealed downregulation of several genes, including NMDA and GABAergic subunits. These effects depended on exposure and sex. The behavioral effects might reflect cognitive inflexibility linked to gene alterations. Further research is needed to clarify these outcomes.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104874"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145575054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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}
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