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Deciphering the TLR-mediated immunotoxic adverse outcome pathway of pentachlorophenol in marine medaka (Oryzias melastigma) tlr介导的五氯酚免疫毒性不良反应通路的解读
IF 8.2 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2025-12-01 DOI: 10.1016/j.enceco.2025.11.039
Yu Zhang , Jizhuang Chu , Shixuan Cui , Qiang Kong , Lihua Cui , Yumiao Zhou , Shudi Yao , Youru Zhang , Huanxin Zhang
Pentachlorophenol (PCP) is a persistent organic pollutant commonly detected in marine environments, and recent studies have confirmed its adverse effects on the immune systems of aquatic organisms. However, the potential molecular mechanisms of action and subsequent downstream damage caused by PCP remain unclear. This study employed transcriptomics, metabolomics, biochemical and histopathological analyses, and molecular dynamics simulations to explore the immunotoxic effects and associated downstream damage induced by PCP in marine medaka (Oryzias melastigma). The results indicated that PCP at environmentally relevant concentrations (1 and 10 μg/L) activates the Toll-like receptor (TLR) signaling pathway, significantly upregulating the expression levels of pro-inflammatory cytokines and triggering inflammatory responses. Using the adverse outcome pathway (AOP) analysis framework, the binding of PCP to TLR5 was identified as the molecular initiating event. This event triggers a series of key events, activation of the TLR signaling pathway, an enhanced inflammatory response, increased oxidative stress levels, disrupted amino acid metabolism, and liver injury, ultimately leading to impaired immune system function (adverse outcome). This study establishes the mechanistic linkage between TLR5 and metabolic dysfunction in PCP immunotoxicity, providing novel toxicological insights and theoretical support for the ecological risk assessment of PCP and related marine pollutants.
五氯酚(PCP)是海洋环境中常见的持久性有机污染物,近年来的研究证实了其对水生生物免疫系统的不良影响。然而,PCP潜在的分子作用机制和随后引起的下游损害尚不清楚。本研究采用转录组学、代谢组学、生化和组织病理学分析以及分子动力学模拟等方法,探讨了PCP对海洋藻(Oryzias melastigma)的免疫毒性作用和相关的下游损伤。结果表明,环境相关浓度(1和10 μg/L)的PCP可激活toll样受体(TLR)信号通路,显著上调促炎细胞因子的表达水平,引发炎症反应。利用不良结果通路(adverse outcome pathway, AOP)分析框架,确定PCP与TLR5的结合为分子启动事件。该事件触发一系列关键事件,TLR信号通路激活,炎症反应增强,氧化应激水平升高,氨基酸代谢中断,肝损伤,最终导致免疫系统功能受损(不良结果)。本研究建立了TLR5与PCP免疫毒性代谢功能障碍之间的机制联系,为PCP及相关海洋污染物的生态风险评估提供了新的毒理学见解和理论支持。
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引用次数: 0
Influencing mechanisms of multiple factors on seasonal variation of atmospheric polybrominated diphenyl ethers and their internal exposure risk in cold region 寒区大气多溴联苯醚季节变化的多因素影响机制及其内暴露风险
IF 8.2 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2025-11-29 DOI: 10.1016/j.enceco.2025.11.034
Meng Qin , Wan-Li Ma , Chuan-Long Zhang , Li-Yan Liu , Pu-Fei Yang
Atmospheric pollutants exhibit seasonal variations in their concentrations and associated exposure risk due to seasonal alternations. The influencing mechanisms of multiple factors on the seasonal variation of concentration of polybrominated diphenyl ethers (PBDEs) in atmosphere were studied in cold region of China by a multimedia fugacity model (S-L4MF Model). The significant seasonal variations were found: gaseous PBDEs exhibited higher concentration in summer and lower concentration in winter, while particulate PBDEs presented opposite trend. The influencing mechanisms of eight key driving factors on PBDEs concentrations were identified that zonal wind, air emission and snow as predominant factors governing gaseous concentration fluctuations, whereas air temperature, TSP and precipitation emerged as primary factors on particulate concentration variations. Subsequently, the seasonal differences in internal exposure risk of PBDEs were investigated by constructing a fugacity-based human model. Similarly, the internal exposure risk of PBDEs also presented seasonal variations. Notably, the internal exposure risk of particulate PBDEs demonstrated distinct size-distribution characteristics: the unimodal pattern in summer versus the bimodal pattern in winter. The study provided new insights into the understanding of seasonal variations and influencing mechanisms of atmospheric pollutants, which provided significant implications for developing seasonal-specific risk assessment frameworks.
大气污染物的浓度和因季节变化而产生的相关暴露风险呈现季节性变化。采用多媒体逸度模型(S-L4MF模型)研究了多因素对中国寒区大气中多溴联苯醚(PBDEs)浓度季节变化的影响机制。其中,气态多溴二苯醚的浓度表现为夏季较高,冬季较低,而颗粒物多溴二苯醚的浓度则呈现相反的趋势。8个关键驱动因素对多溴二苯醚浓度的影响机制表明,纬向风、大气排放和降雪是影响气体浓度波动的主要因素,而气温、总悬浮颗粒物和降水是影响颗粒物浓度变化的主要因素。随后,通过构建基于逸度的人体模型,研究了多溴二苯醚内部暴露风险的季节性差异。同样,多溴二苯醚的内部暴露风险也存在季节性变化。值得注意的是,多溴二苯醚颗粒的内部暴露风险表现出明显的大小分布特征:夏季为单峰模式,冬季为双峰模式。该研究为了解大气污染物的季节变化和影响机制提供了新的见解,这对制定季节性风险评估框架具有重要意义。
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引用次数: 0
Source analysis of heavy metals in groundwater of centralized drinking water sources and seasonal variations of health risks in Wuzhou City, Pearl River Delta, China 珠江三角洲梧州市集中饮用水源地下水重金属来源分析及健康风险季节变化
IF 8.2 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2025-11-28 DOI: 10.1016/j.enceco.2025.11.026
Kunlong Hui , Wenxiang Hu , Beidou Xi , Ying Yuan , Haojie Lu , Wenbing Tan
Groundwater serves as a critical source for centralized drinking water, particularly in rapidly urbanizing regions, yet its quality is increasingly threatened by heavy metals (HMs) pollution. Systematic assessments that integrate source apportionment with seasonal health risks in such settings remain limited, hindering the development of targeted protection strategies. To assess the pollution characteristics and potential health risks of HMs in groundwater in Wuzhou City, Pearl River Delta, a total of 198 groundwater samples were collected for systematic analysis during the wet season and dry season in this study. The results show that the average concentrations of Mn, Fe and Zn are the highest in the two seasons, and Mn, Fe and As often exceed the Class III water limit. Overall, the pollution level of HMs is relatively high during the dry season. Three sources of HMs were identified by principal component analysis and the absolute principal component score - multiple linear regression model: geological background (28.67 % in the dry season and 21.45 % in the wet season), mining activities (22.70 % in the dry season and 26.52 % in the wet season), and agricultural activities (24.08 % in the dry season and 32.23 % in the wet season). The calculation results of the HMs pollution index show that the average HMs pollution index during the dry season and the wet season are 18.0 and 16.1 respectively, further confirming that groundwater pollution is more prominent during the dry season. Health risk assessment and Monte Carlo simulation indicate that the non-carcinogenic risk of children is slightly higher than that of adults. The spatial distribution characteristics indicate that the health risks in the northwest of the study area are more severe. Based on the comprehensive pollution characteristics and risk assessment results, Mn, Fe and As were identified as characteristic pollutants that need to be prioritized for control. The results of this study can provide scientific support for the precise control and treatment of heavy metal pollution in groundwater in Wuzhou City, Pearl River Delta, and at the same time offer an important reference for the formulation of drinking water safety guarantee strategies in similar urbanized areas.
地下水是集中饮用水的重要来源,特别是在快速城市化的地区,但其质量日益受到重金属污染的威胁。在这种情况下,将污染源分析与季节性健康风险结合起来的系统评估仍然有限,阻碍了制定有针对性的保护战略。为评价珠江三角洲梧州市地下水中HMs的污染特征及潜在健康风险,本研究在枯水季和丰水季共采集198份地下水样本进行系统分析。结果表明:两个季节Mn、Fe和Zn的平均浓度最高,Mn、Fe和As经常超过III类限水。总体而言,枯水期的污染程度较高。通过主成分分析和绝对主成分评分-多元线性回归模型,确定了3个HMs来源:地质背景(旱季28.67%,雨季21.45%)、采矿活动(旱季22.70%,雨季26.52%)和农业活动(旱季24.08%,雨季32.23%)。HMs污染指数计算结果表明,枯水季和丰水季的平均HMs污染指数分别为18.0和16.1,进一步证实了地下水污染在枯水季更为突出。健康风险评估和蒙特卡罗模拟表明,儿童的非致癌风险略高于成人。空间分布特征表明,研究区西北部健康风险较为严重。根据综合污染特征和风险评价结果,确定Mn、Fe和As为需要优先控制的特征污染物。研究结果可为珠江三角洲梧州市地下水重金属污染的精准控制与治理提供科学支撑,同时为类似城市化地区饮用水安全保障策略的制定提供重要参考。
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引用次数: 0
Assessing the health risks of environmentally relevant concentrations of fluoride and phenanthrene: Neurobehavioral toxicity induced in zebrafish through disruption of the microbiome-gut-brain axis and suppression of Wnt/β-catenin signalling 评估环境相关氟化物和菲浓度的健康风险:通过破坏微生物群-肠-脑轴和抑制Wnt/β-连环蛋白信号传导在斑马鱼中诱导的神经行为毒性
IF 8.2 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2025-11-27 DOI: 10.1016/j.enceco.2025.11.035
Hongmin Lu , Ruoqi Wang , Xin Zhang, Yuze Dong, Hao Liu, Yunfan Zhang, Chengxue Ma, Mingwei Xing
Chronic exposure to fluoride and phenanthrene is recognized as a significant risk factor for neurobehavioral toxicity, and the gut-brain axis has been identified as a key mechanism in the development of anxiety behaviors following prolonged toxic insult. Nevertheless, the connections between gut microbiota disruption, serotonin (5-HT) production, and neurobehavioral toxicity induced by long-term co-exposure to fluoride and phenanthrene remain unclear. In this study, co-exposure model of phenanthrene and fluoride at environmentally relevant concentrations was established in zebrafish. Through comparative database analysis, anxiety behavior tests, 16S rRNA sequencing, metabolomics, qPCR, Western blotting, ELISA, flow cytometry, comet assay, histological analysis, and immunohistochemistry, the neurotoxic effects of fluoride or/and phenanthrene were investigated. In this study, neurobehavioral toxicity was observed in zebrafish following co-exposure to environmentally relevant concentrations of fluoride and phenanthrene, characterized by diminished swimming capacity and heightened anxiety behavior. The toxic mechanism was mediated through disruption of the microbiome–gut–brain axis homeostasis and suppression of the Wnt/β-catenin signalling pathway. Specifically, co-exposure decreased intestinal synthesis of 5-HT and impaired the blood–brain barrier. As the intestine serves as the primary source of 5-HT, its impairment (histopathological alterations, gut microbiota dysbiosis and metabolomics) led to dysregulation of the 5-HT system. Histopathological analysis of brain tissue revealed synaptic loss, nuclear pyknosis, and the presence of apoptotic bodies. Investigations into the molecular mechanisms indicated that fluoride or/and phenanthrene inhibited Wnt signalling, promoted β-catenin degradation, and induced neurological dysfunction, as evidenced by reductions in SYP and MAP2, which subsequently activated pro-apoptotic genes (Bax, Caspase9, and Caspase3) and inflammatory responses (decreased IL-10, elevated NF-κB, IL-6, TNF-α, and cleaved IL-1β). These alterations ultimately contributed to neurobehavioral deficits. Collectively, these findings indicate that fluoride and phenanthrene induce anxiety behavior and neurotoxicity, associated with perturbations in 5-HT metabolism, gut microbiota composition, oxidative stress, apoptosis, and neuroinflammation.
长期暴露于氟化物和菲被认为是神经行为毒性的重要危险因素,肠-脑轴已被确定为长期毒性损伤后焦虑行为发展的关键机制。然而,肠道菌群破坏、血清素(5-羟色胺)产生和长期暴露于氟化物和菲引起的神经行为毒性之间的联系尚不清楚。在本研究中,建立了环境相关浓度的菲和氟在斑马鱼体内的共暴露模型。通过比较数据库分析、焦虑行为测试、16S rRNA测序、代谢组学、qPCR、Western blotting、ELISA、流式细胞术、comet测定、组织学分析和免疫组织化学等方法,研究氟化物或/和菲的神经毒性作用。在这项研究中,观察到斑马鱼在暴露于环境相关浓度的氟化物和菲后的神经行为毒性,其特征是游泳能力下降和焦虑行为加剧。毒性机制是通过破坏微生物群-肠-脑轴稳态和抑制Wnt/β-catenin信号通路介导的。具体来说,共暴露降低了肠道5-羟色胺的合成并损害了血脑屏障。由于肠道是5-羟色胺的主要来源,其损伤(组织病理学改变,肠道微生物群失调和代谢组学)导致5-羟色胺系统失调。脑组织的组织病理学分析显示突触丢失,核固缩和凋亡小体的存在。对分子机制的研究表明,氟或/和菲抑制Wnt信号传导,促进β-catenin降解,诱导神经功能障碍,SYP和MAP2的减少证明了这一点,这随后激活促凋亡基因(Bax, Caspase9和Caspase3)和炎症反应(降低IL-10,升高NF-κB, IL-6, TNF-α和裂解IL-1β)。这些改变最终导致了神经行为缺陷。综上所述,这些发现表明氟和菲可诱导焦虑行为和神经毒性,并与5-羟色胺代谢、肠道菌群组成、氧化应激、细胞凋亡和神经炎症的紊乱有关。
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引用次数: 0
Distinct bacterial community structure, assembly and functions between aged and multiple petroleum-contaminated sites 不同的细菌群落结构,组装和功能之间的老化和多重石油污染场地
IF 8.2 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2025-11-27 DOI: 10.1016/j.enceco.2025.11.036
Tingting Teng , Xinzi Wang , Yueqiao Liu , Xiaohui Zhao , Yujiao Sun , Aizhong Ding , Jiayuan Pan , Dayi Zhang
Petroleum contamination threatens soil ecosystems, but microbial responses in multi-contaminated area (MCA) and aged-contaminated area (ACA) remain unclear. This study compared bacterial communities in MCA and ACA at China's Lanzhou Petrochemical Site using 16S rRNA sequencing, network analysis and PICRUSt2. MCA had 12-fold higher total petroleum hydrocarbons than ACA, and MAHs and PAHs in MCA were 201-fold and 10-fold higher. PAHs drove bacterial communities in MCA, while those in ACA were shaped by ecological toxicity assessed by whole-cell bioreporter. The network structure of MCA was complex (more modules, positive edges and keystone taxa), whereas that of ACA was relatively simplified. Bacterial community assembly in MCA involved both stochastic (83.09 %) and deterministic (16.91 %) processes, whereas there was only stochastic process in ACA. Bacteria in MCA exhibited stronger carbohydrate metabolic capabilities related to fresh hydrocarbon utilization, whereas those in ACA were more inclined toward amino acid metabolism and membrane transport functions. Our study provides a thorough exploration of soil bacterial response and assembly mechanisms under various petroleum pollution scenarios, offering guidance for developing customized bioremediation strategies in oil-contaminated environments.
石油污染对土壤生态系统构成威胁,但多重污染区(MCA)和老污染区(ACA)的微生物反应尚不清楚。本研究利用16S rRNA测序、网络分析和PICRUSt2比较了中国兰州石化基地MCA和ACA的细菌群落。MCA的总石油烃含量是ACA的12倍,MAHs和PAHs分别是ACA的201倍和10倍。多环芳烃驱动MCA中的细菌群落,而ACA中的细菌群落则由全细胞生物报告器评估的生态毒性形成。MCA网络结构复杂(模块多、正边多、重点类群多),而ACA网络结构相对简化。细菌群落的聚集既有随机过程(83.09%),也有确定性过程(16.91%),而ACA只有随机过程。MCA中的细菌表现出更强的碳水化合物代谢能力,与新鲜碳氢化合物的利用有关,而ACA中的细菌更倾向于氨基酸代谢和膜运输功能。我们的研究深入探索了不同石油污染情景下土壤细菌的响应和组装机制,为开发石油污染环境下的定制生物修复策略提供指导。
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引用次数: 0
The hidden mediator between polycyclic aromatic hydrocarbon exposure and cognitive function of elder adults: FT3/FT4 ratio 多环芳烃暴露与老年人认知功能的隐藏中介:FT3/FT4比值
IF 8.2 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2025-11-27 DOI: 10.1016/j.enceco.2025.11.038
Yafei Gao , Chenran Cai , Han Li , Lu Cheng , Hongkai Zhu , Hongwen Sun , Yang Peng , Hongzhi Zhao
Polycyclic aromatic hydrocarbons (PAHs) are neurotoxicants that may induce cognitive deficits via thyroid dysfunction. Older adults, due to physiological decline, are more susceptible to such toxicants. This cross-sectional study involving 433 elderly adults examined the relationships between PAH exposure, cognitive decline and thyroid-mediated pathways. Urinary PAH metabolites were measured and cognitive performance was assessed using the Mini-Mental State Examination (MMSE). Participants were categorized into low-risk (n = 367) and high-risk mild cognitive impairment (MCI) groups (n = 66) based on MMSE scores. Logistic regression results indicated that the odds of MCI risk increased with each one-unit increase in log-transformed levels of 2-OHNap, 2-OHFlu, and 3-OHFlu. Linear modeling further revealed that these metabolites (OH-Nap and OH-Flu) were dose-dependently negatively associated with orientation, attention and memory. In addition, there was a nonlinear dose-response relationship between 1-OHNap and verbal ability, and ΣOH-PAHs and attention/memory. Critically, mediating effect analysis showed that the FT3/FT4 ratio mediated the association between PAH metabolites and MMSE scores with a contribution of 22.5 %–26.3 %. This study reveals the mechanism by which PAHs exposure may mediate cognitive decline in the elderly by interfering with thyroid function, providing an important scientific basis for the prevention of environmental factor-induced neurodegenerative diseases.
多环芳烃(PAHs)是一种神经毒物,可通过甲状腺功能障碍引起认知障碍。老年人由于生理机能衰退,更容易受到这类毒物的影响。这项横断面研究涉及433名老年人,研究了多环芳烃暴露、认知能力下降和甲状腺介导途径之间的关系。测量尿多环芳烃代谢物,并使用简易精神状态检查(MMSE)评估认知能力。根据MMSE评分将参与者分为低危(n = 367)和高危轻度认知障碍(MCI)组(n = 66)。Logistic回归结果显示,2-OHNap、2-OHFlu和3-OHFlu的对数转化水平每增加一个单位,MCI风险的几率就会增加。线性模型进一步揭示了这些代谢物(OH-Nap和OH-Flu)与定向、注意力和记忆呈剂量依赖性负相关。此外,1-OHNap与语言能力、ΣOH-PAHs与注意/记忆之间存在非线性剂量-反应关系。重要的是,中介效应分析显示,FT3/FT4比率介导了多环芳烃代谢物与MMSE评分之间的关联,贡献率为22.5% - 26.3%。本研究揭示了多环芳烃暴露通过干扰甲状腺功能介导老年人认知能力下降的机制,为预防环境因素诱发的神经退行性疾病提供了重要的科学依据。
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引用次数: 0
Time-dependent toxicity and key toxic components of five neonicotinoid mixtures under environmental concentrations in the Yangtze River Basin 长江流域环境浓度下5种新烟碱混合物的时间依赖性毒性及关键毒性成分
IF 8.2 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2025-11-26 DOI: 10.1016/j.enceco.2025.11.031
Ting-Ting Ding , Xiao-Yu Wang , Shi-Lin Du , Hong-Yi Liang , Ya-Hui Zhang , Jin Zhang , Ming-Xiao Li , Shu-Shen Liu
Neonicotinoids (NEOs), as widely used insecticides, have raised increasing concerns regarding their ecological impacts. Current knowledge on the mixture toxicity of NEOs, particularly under environmental concentrations, remains insufficient. This study investigated the occurrence of five representative NEOs, including imidacloprid (IMI), thiamethoxam (THM), clothianidin (CLO), acetamiprid (ACE), and thiacloprid (THA), in surface water from the Linjiang (LJ) and Xuebu (XB) River Basins within the Yangtze River Basin. The total concentrations of the five NEOs ranged from 0.16 to 72.31 ng/L, with higher levels detected in the LJ Basin. High-throughput microplate toxicity analysis showed that the single THA and THM exhibited stimulatory effects (−17 % to 47 %) on Vibrio qinghaiensis sp.-Q67 (Q67). The 72 mixtures of the five NEOs exhibited not only inhibitory effects (up to 34 %) on Q67 at 12 h but also previously unobserved stimulatory effects (down to −32 %). These mixtures showed three different time-dependent toxicity characteristics during 0.25–12 h: 23 mixtures consistently exhibited stimulatory effects, 30 mixtures shifted from stimulatory to no effect, and 19 mixtures shifted from no effect to inhibitory effects. CLO, although showing no direct effect as a single compound, was identified as a key driver influencing mixture toxicity, exhibiting interactions with other components. Ecological risk assessment indicated that IMI, THM, CLO, and ACE posed potential ecological risks in the LJ Basin (risk quotients≥0.1). Based on the findings, management of NEOs in the LJ Basin may need to be strengthened, with particular attention to CLO due to its single ecological risk and key driver influencing mixture toxicity. This study provides comprehensively understanding of single and mixture toxicities of NEOs at environmental concentrations.
新烟碱类杀虫剂作为一种广泛使用的杀虫剂,其生态影响日益引起人们的关注。目前关于近地天体的混合毒性,特别是在环境浓度下的毒性的知识仍然不足。研究了长江流域临江和学布两河流域地表水中吡虫啉(IMI)、噻虫嗪(THM)、噻虫苷(CLO)、啶虫啉(ACE)和噻虫啉(THA) 5种代表性neo的赋存情况。5种近地天体的总浓度范围为0.16 ~ 72.31 ng/L,其中LJ盆地的近地天体浓度较高。高通量微孔板毒力分析显示,单药对青岛弧菌sp.-Q67 (Q67)的刺激作用为- 17% ~ 47%。5种neo的72种混合物在12 h时不仅表现出对Q67的抑制作用(高达34%),而且还表现出先前未观察到的刺激作用(降至- 32%)。这些混合物在0.25 ~ 12 h内表现出三种不同的时间依赖性毒性特征:23种混合物始终表现出刺激作用,30种混合物从刺激作用转变为无作用,19种混合物从无作用转变为抑制作用。CLO虽然作为单一化合物没有直接作用,但被确定为影响混合物毒性的关键驱动因素,表现出与其他成分的相互作用。生态风险评价表明,IMI、THM、CLO和ACE构成LJ流域潜在生态风险(风险商≥0.1)。基于这些发现,LJ盆地近地天体的管理可能需要加强,特别是CLO,因为它具有单一的生态风险和影响混合毒性的关键驱动因素。本研究全面了解了环境浓度下neo的单一毒性和混合毒性。
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引用次数: 0
First in situ application of a non-invasive sampling approach to assess pesticide effects on amphibian enzymatic activities 首先在现场应用非侵入性采样方法来评估农药对两栖动物酶活性的影响
IF 8.2 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2025-11-26 DOI: 10.1016/j.enceco.2025.11.028
Alexandre J.W. Michel , Julie Tonial , Soline Bettencourt-Amarante , Cédric Chaumont , Mathieu Girondin , Julien Tournebize , Alienor Jeliazkov , Jérémie D. Lebrun
Amphibians are particularly vulnerable to pesticide exposures, according to numerous laboratory and field studies. Enzymatic activities in biological tissues and body condition are usually proposed as relevant biomarkers for studying the effects of pesticides on these organisms, especially in agricultural context. Nevertheless, measuring enzymatic activities in animals often requires invasive sampling methods, such as blood sampling or destruction of individuals, in the case of juveniles in particular. Limiting the harmful effects of invasive methods and developing non-invasive approaches is crucial to the ethical principles that aim to minimize the impact on individuals. We aimed to test a non-invasive sampling approach, namely buccal swabbing, to investigate the effects of pesticides on the enzymatic activities of two native amphibian species, the common toad (Bufo bufo) and the green frog (Pelophylax sp.), in six ponds distributed along a pesticide contamination gradient. We also performed morphometric measurements to determine the body condition of the swabbed individuals. Our results show that buccal swabbing effectively allows quantifying the activities of 6 enzymes present in the saliva of wild amphibians and involved in neurological, non-specific immunity, and nutrition processes, supporting the relevance of this approach to assess their enzymatic responses in situ. Enzymatic levels of acetylcholinesterase, β-galactosidase, and β-glucosidase, as well as cytotoxic biomarkers, such as glutathione S-transferase, and peroxidases, were either significantly correlated with pesticide concentrations, or responsive to synchronic-antagonistic effects of pesticide fluxes occurring in an agricultural constructed wetland. These results suggest that buccal swabbing in amphibians is applicable in the field for this purpose and that agricultural constructed wetlands could have the potential to affect aquatic fauna. Body condition was similar between ponds, regardless of the pesticide pressure level, probably because this variable reacts on longer time scales than enzymatic activities, or because of absence of effects, especially as this trait may be driven by other environmental factors. Our study highlights the relevance of using buccal swabbing to study the effects of pesticides on amphibians in the field while having limited impacts on animal welfare.
根据大量的实验室和实地研究,两栖动物特别容易受到农药的影响。生物组织中的酶活性和身体状况通常被认为是研究农药对这些生物的影响的相关生物标志物,特别是在农业环境中。然而,测量动物体内的酶活性通常需要侵入性的采样方法,例如血液采样或破坏个体,特别是在幼体的情况下。限制侵入性方法的有害影响和发展非侵入性方法对于旨在尽量减少对个人影响的伦理原则至关重要。在沿农药污染梯度分布的6个池塘中,研究了农药对两种本地两栖动物——蟾蜍(Bufo Bufo)和绿蛙(Pelophylax sp.)——酶活性的影响,采用非侵入性取样方法,即口腔拭子取样。我们还进行了形态计量测量,以确定拭子个体的身体状况。我们的研究结果表明,口腔拭子可以有效地量化野生两栖动物唾液中6种酶的活性,这些酶参与神经、非特异性免疫和营养过程,支持这种方法在原位评估它们的酶反应的相关性。乙酰胆碱酯酶、β-半乳糖苷酶和β-葡萄糖苷酶的酶水平,以及细胞毒性生物标志物,如谷胱甘肽s -转移酶和过氧化物酶,要么与农药浓度显著相关,要么对农业人工湿地中农药通量的同步拮抗作用有反应。这些结果表明,在两栖动物的口腔拭子是适用于这一目的的现场和农业人工湿地可能有影响水生动物的潜力。无论农药压力水平如何,池塘之间的体况相似,可能是因为该变量的反应时间比酶活性长,或者因为没有影响,特别是由于该性状可能由其他环境因素驱动。我们的研究强调了使用口腔拭子来研究农药对野外两栖动物的影响的相关性,同时对动物福利的影响有限。
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引用次数: 0
New Approach Methodologies (NAMs) reveal triphenyl phosphate (TPP) disrupts lipid metabolism in estuarine fish via PPARγ activation: A concentration-dependent transcriptomic and molecular docking study 新方法方法(NAMs)揭示磷酸三苯酯(TPP)通过PPARγ激活破坏河口鱼类的脂质代谢:一项浓度依赖性转录组学和分子对接研究
IF 8.2 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2025-11-26 DOI: 10.1016/j.enceco.2025.11.037
Jinzhi Ren , Ying Peng , Chenyang Sun , Yining Zhang , Jianjun Li , Simin Xia , Caixia Gao , Yimeng Wang , Xiangping Nie
There is an urgent need for a more efficient and ethical approach to chemical toxicity assessment. The emergence of New Approach Methodologies (NAMs) based on fish embryos transcriptomics provides a promising alternative. Triphenyl phosphate (TPP) — a pervasive contaminant in estuaries — disrupts lipid homeostasis in mammals via PPARγ activation, yet its ecotoxicological impacts on estuarine fish remain unknown. Leveraging NAMs, this study integrates concentration-dependent transcriptomics (CDT), molecular docking, and phenotypic toxicity assays to unravel effects of TPP on embryonic development and lipid metabolism in the benthic fish Mugilogobius chulae. We found that TPP induced significant lethality (LC₅₀ = 1.86 × 106 ng/L) and teratogenicity (EC₅₀ = 5.27 × 105 ng/L), suppressing spontaneous movement, heart rate, and hatching. At concentrations of 5270 ng/L and 52,700 ng/L, TPP elevated triglycerides, total cholesterol, and hepatotoxicity markers (alanine aminotransferase / aspartate aminotransferase). CDT analysis identified fatty acid metabolism pathways as the most sensitive targets, with TPP upregulating PPARγ while downregulating CD36 and ACSL5 — indicating blocked fatty acid oxidation and explaining lipid accumulation. Crucially, co-exposure with PPARγ antagonist GW9662 reversed metabolic disorders, validating the mechanistic role of PPARγ. Furthermore, molecular docking confirmed that TPP binds PPARγ with agonist-like affinity. This work establishes a NAM-based framework for deciphering the toxicity of contaminants of emerging concern in estuarine ecosystems, offering novel tools for ecological risk assessment.
迫切需要一种更有效和合乎道德的方法来进行化学毒性评估。基于鱼类胚胎转录组学的新方法方法(NAMs)的出现提供了一个有希望的替代方案。磷酸三苯酯(TPP)是河口中普遍存在的污染物,通过激活PPARγ破坏哺乳动物的脂质稳态,但其对河口鱼类的生态毒理学影响尚不清楚。利用NAMs,本研究整合了浓度依赖性转录组学(CDT)、分子对接和表型毒性分析,以揭示TPP对底栖鱼类马基洛gobius chulae胚胎发育和脂质代谢的影响。我们发现TPP诱导了显著的致死率(LC₅₀= 1.86 × 106 ng/L)和致畸性(EC₅₀= 5.27 × 105 ng/L),抑制了自发运动、心率和孵化。在5270 ng/L和52700 ng/L浓度下,TPP升高了甘油三酯、总胆固醇和肝毒性标志物(丙氨酸转氨酶/天冬氨酸转氨酶)。CDT分析发现,脂肪酸代谢途径是最敏感的靶点,TPP上调PPARγ,下调CD36和ACSL5,这表明脂肪酸氧化受阻,并解释了脂质积累。至关重要的是,与PPARγ拮抗剂GW9662共同暴露可逆转代谢紊乱,验证了PPARγ的机制作用。此外,分子对接证实了TPP以类似激动剂的亲和力结合PPARγ。这项工作建立了一个基于nama的框架,用于破译河口生态系统中新兴关注的污染物的毒性,为生态风险评估提供了新的工具。
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引用次数: 0
HFPO-DA and PFOA exert differential combined toxicity with Cd in Paramecium: growth, behavior and molecular insights HFPO-DA和PFOA对草履虫具有不同的Cd联合毒性:生长、行为和分子见解
IF 8.2 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2025-11-25 DOI: 10.1016/j.enceco.2025.11.032
Congjun Li , Yu Fu , Eleni Gentekaki , Lifang Li
Hexafluoropropylene oxide dimer acid (HFPO-DA) has come into use as an alternative to perfluorooctanoic acid (PFOA), but it remains elusive whether their comparative toxicities in aquatic organisms under co-occurring heavy metals like cadmium (Cd), particularly one ecologically important microorganism, the protists. Here, we compared the combined toxicity of PFOA and HFPO-DA in euryhaline ciliate Paramecium duboscqui under Cd-contaminated conditions. Chronic exposure (14 days) to field-realistic concentrations of Cd (50 μg/L) and PFOA/HFPO-DA (1 μg/L) revealed similarly adverse effects on growth performance. When combined with Cd, HFPO-DA caused greater disruption to membrane permeability thus enhancing Cd availability in ciliates, and amplifying oxidative stress and apoptosis activation. Moreover, combining HFPO-DA and Cd significantly reduced the motility distance, mean and max velocity in ciliates compared to PFOA. Transcriptomic analysis consequently revealed that disruptions in the core energy metabolism pathways were likely responsible for the insufficient supply of ATP energy in P. duboscqui. Additionally, the simultaneous downregulation of ciliary motility-related gene set and pathway, with the most pronounced suppression observed under HFPO-DA and Cd co-exposure mechanistically linked transcriptional changes to behavioral consequences. Our findings suggest that the combined effects of PFOA/HFPO-DA and Cd pose compounded ecological risks, underscoring the need to consider PFOA and its alternative HFPO-DA in regulatory frameworks along with heavy metals.
六氟环氧丙烷二聚酸(HFPO-DA)已被用作全氟辛酸(PFOA)的替代品,但它们在镉(Cd)等重金属共存下对水生生物,特别是一种重要的生态微生物原生生物的相对毒性是否存在尚不清楚。本研究比较了cd污染条件下PFOA和HFPO-DA对杜波沙奇草履虫的联合毒性。长期暴露于Cd (50 μg/L)和PFOA/HFPO-DA (1 μg/L)环境(14天)对生长性能的不利影响相似。当与Cd结合时,HFPO-DA对细胞膜渗透性造成更大的破坏,从而提高了Cd在纤毛虫体内的可用性,并放大了氧化应激和细胞凋亡激活。此外,与PFOA相比,HFPO-DA和Cd联合使用显著降低了纤毛虫的运动距离、平均速度和最大速度。转录组学分析结果显示,核心能量代谢途径的中断可能是导致P. duboscqui ATP能量供应不足的原因。此外,纤毛运动相关基因组和通路的同时下调,在HFPO-DA和Cd共暴露下观察到最明显的抑制,机制上将转录变化与行为后果联系起来。我们的研究结果表明,PFOA/HFPO-DA和Cd的综合影响构成了复杂的生态风险,强调了在监管框架中考虑PFOA及其替代HFPO-DA和重金属的必要性。
{"title":"HFPO-DA and PFOA exert differential combined toxicity with Cd in Paramecium: growth, behavior and molecular insights","authors":"Congjun Li ,&nbsp;Yu Fu ,&nbsp;Eleni Gentekaki ,&nbsp;Lifang Li","doi":"10.1016/j.enceco.2025.11.032","DOIUrl":"10.1016/j.enceco.2025.11.032","url":null,"abstract":"<div><div>Hexafluoropropylene oxide dimer acid (HFPO-DA) has come into use as an alternative to perfluorooctanoic acid (PFOA), but it remains elusive whether their comparative toxicities in aquatic organisms under co-occurring heavy metals like cadmium (Cd), particularly one ecologically important microorganism, the protists. Here, we compared the combined toxicity of PFOA and HFPO-DA in euryhaline ciliate <em>Paramecium duboscqui</em> under Cd-contaminated conditions. Chronic exposure (14 days) to field-realistic concentrations of Cd (50 μg/L) and PFOA/HFPO-DA (1 μg/L) revealed similarly adverse effects on growth performance. When combined with Cd, HFPO-DA caused greater disruption to membrane permeability thus enhancing Cd availability in ciliates, and amplifying oxidative stress and apoptosis activation. Moreover, combining HFPO-DA and Cd significantly reduced the motility distance, mean and max velocity in ciliates compared to PFOA. Transcriptomic analysis consequently revealed that disruptions in the core energy metabolism pathways were likely responsible for the insufficient supply of ATP energy in <em>P. duboscqui</em>. Additionally, the simultaneous downregulation of ciliary motility-related gene set and pathway, with the most pronounced suppression observed under HFPO-DA and Cd co-exposure mechanistically linked transcriptional changes to behavioral consequences. Our findings suggest that the combined effects of PFOA/HFPO-DA and Cd pose compounded ecological risks, underscoring the need to consider PFOA and its alternative HFPO-DA in regulatory frameworks along with heavy metals.</div></div>","PeriodicalId":100480,"journal":{"name":"Environmental Chemistry and Ecotoxicology","volume":"8 ","pages":"Pages 339-351"},"PeriodicalIF":8.2,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Environmental Chemistry and Ecotoxicology
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