Aquatic Toxicology最新文献_第9页

Hepatic cyp24a1 serves as a biomarker for diagnosing polystyrene microplastic exposure in Nile tilapia (Oreochromis niloticus) 肝脏cyp24a1可作为尼罗罗非鱼聚苯乙烯微塑料暴露诊断的生物标志物

IF 4.3 2区环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY

Aquatic Toxicology

Pub Date : 2025-11-15 DOI: 10.1016/j.aquatox.2025.107649

Feilong Wang , Haiyan Xu , Xiaomeng Guo , Xiaolong Fan , Yuanyuan Li , Tiao Gao , Xin Xie , Na Guo , Fan Bai , Yixin Chen , Changle Zhao , Deshou Wang , Lina Sun , Fengrui Wu

Microplastics (MPs), particularly polystyrene (PS), pose a significant threat to aquatic ecosystems globally. Sensitive biomarkers for diagnosing PS exposure are critical for environmental monitoring, yet evolutionarily conserved diagnostic markers in fish remain poorly characterized. This study identified cytochrome P450 (CYP) superfamily members as potential biomarkers for PS exposure in Nile tilapia (Oreochromis niloticus), a globally farmed species and established toxicological model. We comprehensively characterized 88 CYP genes using whole-genome and multi-tissue transcriptomic analyses. Hepatic transcriptional responses to 100 nm PS exposure (100 μg/L) were profiled via RNA sequencing across acute (7 days), adaptive (14 days), and sub-chronic (21 days) exposure phases. Candidate biomarkers were validated by qPCR, Western blot, and immunofluorescence, with cross-species conservation assessed across fourteen teleosts. Histology revealed PS-induced hepatocyte nuclear pyknosis. Transcriptomic analysis identified dysregulation of CYP genes, and KEGG enrichment highlighted significant alteration in the cytochrome P450 pathway. Genomic analysis clustered the 88 CYP genes into 17 subfamilies, all harboring conserved P450 domains. Multi-tissue expression profiling (liver, testis, ovary, brain, heart, head kidney, kidney, skeletal muscle) indicated predominant hepatic expression for most CYP genes, aligning with the liver’s metabolic role. Notably, Cyp24a1 exhibited sustained upregulation across all exposure phases, validated at the protein level. Immunofluorescence localized Cyp24a1 expression specifically to hepatic adipocytes. Phylogenetic analysis confirmed cyp24a1 conservation within teleosts. We propose hepatic cyp24a1 as a potential biomarker for diagnosing PS exposure in fish, with its early and persistent induction suggesting its potential utility for environmental monitoring.

微塑料（MPs），特别是聚苯乙烯（PS），对全球水生生态系统构成重大威胁。诊断PS暴露的敏感生物标志物对环境监测至关重要，但鱼类中进化保守的诊断标志物仍然缺乏特征。本研究确定了细胞色素P450 （CYP）超家族成员作为尼罗罗非鱼（Oreochromis niloticus）暴露于PS的潜在生物标志物，尼罗罗非鱼是全球养殖物种，并建立了毒理学模型。我们使用全基因组和多组织转录组学分析全面表征了88个CYP基因。通过RNA测序分析了100 nm PS （100 μg/L）暴露在急性（7天）、适应性（14天）和亚慢性（21天）暴露阶段的肝脏转录反应。候选生物标志物通过qPCR、Western blot和免疫荧光验证，并评估了14种硬骨鱼的跨物种保护性。组织学显示ps诱导的肝细胞核固缩。转录组学分析发现CYP基因失调，KEGG富集突出了细胞色素P450通路的显著改变。基因组分析将88个CYP基因聚集到17个亚家族中，所有亚家族都含有保守的P450结构域。多组织表达谱（肝脏、睾丸、卵巢、大脑、心脏、头肾、肾、骨骼肌）显示，大多数CYP基因在肝脏的主要表达，与肝脏的代谢作用一致。值得注意的是，Cyp24a1在所有暴露阶段都表现出持续的上调，这在蛋白质水平上得到了验证。免疫荧光将Cyp24a1的表达特异性定位于肝脂肪细胞。系统发育分析证实了在硬骨鱼中cyp24a1的保守性。我们提出肝脏cyp24a1作为诊断鱼类PS暴露的潜在生物标志物，其早期和持久的诱导表明其在环境监测中的潜在效用。

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引用次数: 0

Image-based morphological characterization of the erythrocytic shape of green turtle (Chelonia mydas) for its potential use as an environmental biomarker 基于图像的绿龟红细胞形态特征及其作为环境生物标志物的潜在应用。

IF 4.3 2区环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY

Aquatic Toxicology

Pub Date : 2025-11-12 DOI: 10.1016/j.aquatox.2025.107645

Claudia Lorena Rodríguez-Salazar , Mauricio Comas-García , Javier Flavio Vigueras-Gómez , Claudia G. Castillo , Adriana Monsiváis-Urenda , Tania Zenteno-Savín , Vanessa Labrada-Martagón

Environmental pollutants increase genotoxic damage in green sea turtles (Chelonia mydas). Erythrocytic nuclear abnormalities (ENA) have been identified using the micronucleus (MN) test, a biomarker of DNA damage. The MN test is time-consuming, and counting depends on the observer, who requires training to avoid false positives. This study aimed to evaluate the utility of image-based morphometric measurements of erythrocyte nuclear shape to assess differences among green turtles from the Mexican Caribbean inhabiting four feeding sites with varying levels of anthropogenic pressure. An semi-automated measurement of 350 nuclei per animal (n = 60) per study site (n = 15) was performed, optimizing the traditional, time-consuming process of 1000–2000 cell counts. Eight metrics of the nuclei morphology were obtained and correlated with the frequency of ENA. A non-linear regression analysis was performed at each study site to infer the focus distance (FD) term from the aspect ratio (AR) and to evaluate deviations from the ellipse in cases with nuclear abnormalities. The erythrocyte nuclei’s minor axis, AR, FD, circularity, and roundness were correlated with the number of ENA. The green turtles captured in the most highly anthropized sites (i.e., Akumal and Xcalak) showed the highest frequency of ENA, the smallest area, and the nuclear form most deviated from the elliptical nuclear erythrocytic shape expected. The proposed methodology enabled differentiation of sea turtles’ habitat conditions. Results from this study agree with previous reports of the highest concentrations of organic persistent pollutants, genotoxic damage, and alterations in oxidative stress in green turtles inhabiting urbanized areas of the Mexican Caribbean.

环境污染物增加了绿海龟（Chelonia mydas）的基因毒性损害。红细胞核异常（ENA）已确定使用微核（MN）测试，DNA损伤的生物标志物。MN测试很耗时，计数取决于观察者，观察者需要训练以避免误报。本研究旨在评估基于图像的红细胞核形态测量的实用性，以评估居住在墨西哥加勒比海的绿海龟在四个不同水平的人为压力下的喂养点之间的差异。每个研究地点（n = 15）对每只动物（n = 60） 350个细胞核进行了半自动化测量，优化了传统的耗时的1000-2000个细胞计数过程。获得了细胞核形态学的8个指标，并与ENA频率相关。在每个研究地点进行非线性回归分析，以从纵横比（AR）推断焦点距离（FD）项，并评估核异常情况下与椭圆的偏差。红细胞核的小轴、AR、FD、圆度、圆度与ENA数目相关。在人类活动最频繁的地点（如Akumal和Xcalak）捕获的绿海龟，其ENA频率最高，面积最小，核形状最偏离预期的椭圆形核红细胞形状。所提出的方法能够区分海龟的栖息地条件。这项研究的结果与先前关于居住在墨西哥加勒比海城市化地区的绿海龟中有机持久性污染物浓度最高、基因毒性损伤和氧化应激变化的报道一致。

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引用次数: 0

Metabolic toxicity of PAHs in Ruditapes philippinarum: Metabolic pathways and hepatotoxicity 菲律宾蛤中多环芳烃的代谢毒性：代谢途径和肝毒性

IF 4.3 2区环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY

Aquatic Toxicology

Pub Date : 2025-11-12 DOI: 10.1016/j.aquatox.2025.107643

Qiuhong Xu, Qiaoqiao Wang, Ruyue Ma, Rongjun Cai, Songhui Xie, Jingjing Miao, Luqing Pan

Polycyclic aromatic hydrocarbons (PAHs) are persistent organic pollutants that exhibit high bioaccumulation and toxicity, posing a significant threat to marine ecosystems. This study integrated transcriptomics, computational modeling, and experimental validation to elucidate the detoxification metabolism and hepatotoxicity of a PAHs mixture (phenanthrene: chrysene: benzo[a]pyrene = 1:1:1) in the Manila clam (Ruditapes philippinarum). PAHs exposure activated detoxification genes via aryl hydrocarbon receptor and HR96-like pathways, with additional modulation through neurotransmitter-mediated NF-κB and tyrosine kinase signaling. Phase I (e.g., CYP1A1, CYP3A4) and Phase II enzymes were upregulated, yet persistent reactive oxygen species accumulation caused macromolecular damage. Females exhibited lower detoxification but greater oxidative stress than males. Chronic oxidative injury induced liver impairment, probably accompanied by inflammation and fibrosis. These findings reveal sex-dependent toxicological responses and provide mechanistic insights for ecological risk assessment and biomarker development in marine pollution monitoring.

多环芳烃（PAHs）是具有高生物蓄积性和高毒性的持久性有机污染物，对海洋生态系统构成重大威胁。本研究结合转录组学、计算模型和实验验证来阐明马尼拉蛤（Ruditapes philippinarum）中多环芳烃混合物（菲：芘：苯并[a]芘= 1:1:1）的解毒代谢和肝毒性。多环芳烃暴露通过芳烃受体和hr96样途径激活解毒基因，并通过神经递质介导的NF-κB和酪氨酸激酶信号通路进行额外调节。I期酶（如CYP1A1， CYP3A4）和II期酶上调，但持续的活性氧积累导致大分子损伤。雌性比雄性表现出更低的解毒能力，但更大的氧化应激。慢性氧化损伤引起肝损害，可能伴有炎症和纤维化。这些发现揭示了性别依赖的毒理学反应，并为海洋污染监测中的生态风险评估和生物标志物开发提供了机制见解。

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引用次数: 0

Geosmin and 2-methylisoborneol exposure affects immune-related gene expression in rainbow trout (Oncorhynchus mykiss) 土臭素和2-甲基异龙脑暴露对虹鳟免疫相关基因表达的影响

IF 4.3 2区环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY

Aquatic Toxicology

Pub Date : 2025-11-12 DOI: 10.1016/j.aquatox.2025.107646

L. Polke-Pedersen, K. Kumas, R. Jaafar, P.W. Kania, A.M. Karami, K. Buchmann

The terpenoid compounds geosmin (GSM) and 2-methylisoborneol (MIB), produced by a wide range of microorganisms, are abundant in many aquatic environments. Both compounds are easily detectable by humans (<5 ng/L), and they are often associated with an earthy and musty unpleasant odor in drinking water and aquatic food products (such as fish and shellfish, blue food), which are costly to circumvent. These compounds are well known to bioaccumulate in larger organisms, such as fish, but the interactions between immune responses and these off-flavor compounds are not well known. We evaluated if prior exposure to these compounds can affect immune gene expression in trout. Juvenile (∼9 g) rainbow trout (Oncorhynchus mykiss) were exposed to geosmin and MIB in environmentally relatable concentrations as well as a high concentration (10, 50, 500, 1000 ng/L) for 24 h before IP injection of lipopolysaccharide (LPS) eliciting inflammatory reactions in trout. Following another 24 h fish were euthanized and liver and spleen were sampled for gene expression measurements (qPCR). Both geosmin and MIB significantly altered expression of several immune-related genes in a tissue- and concentration-dependent manner. Geosmin exposure was associated with a dosage dependent down-regulation in the liver of genes encoding cytokines (IL-4/13a, IL-12, TNFα), acute phase proteins (SAA, precerebellin), antimicrobial peptides (cathelicidin 1 and 2), T cell markers (TCR, CD 8), and B cell marker (IgDm). This may have implications for fish in general, but is particularly notable for those living in eutrophicated waters.

萜类化合物土臭素（GSM）和2-甲基异龙脑（MIB）是由多种微生物产生的，在许多水生环境中都很丰富。这两种化合物都很容易被人类检测到（5ng /L），并且它们通常与饮用水和水生食品（如鱼和贝类，蓝色食品）中泥土和发霉的难闻气味有关，这是昂贵的规避。众所周知，这些化合物会在较大的生物体（如鱼）中积累，但免疫反应与这些异味化合物之间的相互作用尚不清楚。我们评估了事先接触这些化合物是否会影响鳟鱼的免疫基因表达。将幼年虹鳟鱼（Oncorhynchus mykiss）暴露在环境相关浓度以及高浓度（10、50、500、1000 ng/L）的土smin和MIB中24小时，然后注射脂多糖（LPS），引起鳟鱼的炎症反应。24 h后，对鱼实施安乐死，取肝脏和脾脏样本进行基因表达测定（qPCR）。土臭素和MIB都以组织和浓度依赖的方式显著改变了几种免疫相关基因的表达。Geosmin暴露与肝脏中编码细胞因子（IL-4/13a、IL-12、TNFα）、急性期蛋白（SAA、precerebellin）、抗菌肽（cathelicidin 1和2）、T细胞标志物（TCR、cd8）和B细胞标志物（IgDm）的基因的剂量依赖性下调有关。这可能对一般鱼类有影响，但对生活在富营养化水域的鱼类尤其明显。

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引用次数: 0

Commercial formulation containing 2,4-Dichlorophenoxyacetic Acid (2,4-D) induces cellular damage, tissue injury, and antioxidant disruption in zebrafish Danio rerio 含有2,4-二氯苯氧乙酸（2,4- d）的商业配方可诱导斑马鱼细胞损伤、组织损伤和抗氧化剂破坏

IF 4.3 2区环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY

Aquatic Toxicology

Pub Date : 2025-11-12 DOI: 10.1016/j.aquatox.2025.107647

Breno Raul Freitas Oliveira , Aline Guimarães Pereira , Rafael Kremer , Gabriel Da Rocha Zurchimitten , Daniele Hummel Moreira , Lucas Cezar Pinheiro , Carmen Simioni , Luciane Cristina Ouriques , Geison Souza Izídio

2,4-Dichlorophenoxyacetic acid (2,4-D) is one of the oldest and most widely used herbicides globally. Although effective as a pesticide, increasing evidence suggests it may exert toxic effects on non-target aquatic organisms. This study aimed to evaluate morphological, ultrastructural, and biochemical changes in the gills of adult zebrafish (Danio rerio) following short-term exposure to commercial formulation containing 2,4-D. Fish were exposed to 0 (control), 0.03, 0.3, and 3.0 mg/L of the herbicide for seven days. After exposure, gills were collected for analysis. Histological examination revealed cellular alterations in the secondary lamellae, including hyperplasia, hypertrophy of pavement and mitochondria-rich cells (MRCs), and epithelial lifting. Histopathological assessment indicated mild damage at 0.3 mg/L and moderate damage at 3.0 mg/L. Ultrastructural analysis showed mitochondrial disruption in MRCs and damage to pillar cells at the highest concentration. Biochemical analyses revealed decreased levels of both reduced glutathione (GSH) and oxidized glutathione (GSSG), along with increased nitrite concentrations in the group exposed to 3.0 mg/L. No lipid peroxidation was detected following herbicide exposure. The combination of elevated nitrite levels, reduced GSH and GSSG, vascular dilation, mitochondrial damage, and inflammatory cell infiltration strongly supports a link between nitric oxide (NO)-mediated inflammation and the vascular lesions observed in the 3.0 mg/L group. These findings demonstrate that the herbicide can compromise gill structure. Taken together, our results underscore the need for stricter environmental regulations and highlight the potential ecological risks associated with the use of commercial formulations containing 2,4-D.

2,4-二氯苯氧乙酸（2,4- d）是世界上最古老、最广泛使用的除草剂之一。虽然作为杀虫剂是有效的，但越来越多的证据表明它可能对非目标水生生物产生毒性作用。本研究旨在评估成年斑马鱼（Danio rerio）短期暴露于含有2,4- d的商业配方后鳃的形态学、超微结构和生化变化。鱼分别暴露于0（对照）、0.03、0.3和3.0 mg/L的除草剂中7天。暴露后，收集鳃进行分析。组织学检查显示继发片层的细胞改变，包括增生、铺装细胞和富含线粒体细胞（MRCs）肥大以及上皮细胞升高。组织病理学检查显示0.3 mg/L轻度损伤，3.0 mg/L中度损伤。超微结构分析显示，高浓度时MRCs线粒体破坏，柱状细胞受损。生化分析显示，暴露于3.0 mg/L剂量组的还原性谷胱甘肽（GSH）和氧化性谷胱甘肽（GSSG）水平均下降，亚硝酸盐浓度升高。除草剂暴露后未检测到脂质过氧化。亚硝酸盐水平升高、GSH和GSSG降低、血管扩张、线粒体损伤和炎症细胞浸润等综合作用，有力地支持了在3.0 mg/L组中观察到的一氧化氮（NO）介导的炎症与血管病变之间的联系。这些发现表明，除草剂可以破坏鳃结构。综上所述，我们的研究结果强调了更严格的环境法规的必要性，并强调了与使用含有2,4- d的商业配方相关的潜在生态风险。

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引用次数: 0

Unravelling effects of resorcinol: Morphological alterations in the retina and thyroid follicles of zebrafish (Danio rerio) embryos 间苯二酚的解旋效应：斑马鱼胚胎视网膜和甲状腺滤泡的形态学改变

IF 4.3 2区环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY

Aquatic Toxicology

Pub Date : 2025-11-10 DOI: 10.1016/j.aquatox.2025.107642

Imen Ben Chabchoubi , Marian Stoll , Maximilian Rinderknecht , Luisa Reger , Laura Behnstedt , Thomas Braunbeck , Lisa Baumann , Olfa Hentati , Lisa Gölz

The hypothalamus-pituitary-thyroid (HPT) axis is a central endocrine regulatory network crucial for morphological development and physiological homeostasis in vertebrates. It is particularly sensitive to disruption by Endocrine Disrupting Chemicals (EDCs), which may lead to adverse effects at the individual and population levels. Resorcinol, an environmentally relevant compound used extensively in industry and cosmetics, has been identified as a potential disruptor of the thyroid hormone system (THS). However, data on its effects in aquatic organisms, especially fish, remain scarce. Recent studies and adverse outcome pathways (AOPs) even suggest a link between thyroid hormone system (THS) disruption and retinal layer alterations in fish. In this study, transgenic Tg(tg:MA-mCherry) zebrafish (Danio rerio) embryos were exposed to resorcinol for 120 h to assess effects on thyroid follicle morphology, retinal development and behaviour. Thyroid follicles were analysed using in vivo fluorescence microscopy. Retinal layers were evaluated histopathologically and behaviour changes were assessed using the light–dark locomotion test. Exposure to 1 and 30 mg/L resorcinol resulted in thyroid follicle proliferation, likely indicating a compensatory response to inhibited thyroid hormone synthesis. At 100 mg/L, reduced eye size and thinning of multiple retinal layers were observed, suggesting secondary developmental effects. Additionally, increased locomotor activity was detected in exposed embryos. These findings support the classification of resorcinol as a THS-disrupting compound and emphasize the need to incorporate histopathological and behaviour endpoints into existing OECD test guidelines to improve the detection of THS disruptors in fish.

下丘脑-垂体-甲状腺（HPT）轴是中枢内分泌调节网络，对脊椎动物的形态发育和生理稳态至关重要。它对内分泌干扰物（EDCs）的干扰特别敏感，这可能导致个人和人群水平的不利影响。间苯二酚是一种广泛应用于工业和化妆品的环保化合物，已被确定为甲状腺激素系统（THS）的潜在干扰物。然而，关于其对水生生物，特别是鱼类的影响的数据仍然很少。最近的研究和不良后果途径（AOPs）甚至表明，甲状腺激素系统（THS）的破坏与鱼类视网膜层的改变之间存在联系。本研究将转基因Tg（Tg:MA-mCherry）斑马鱼（Danio rerio）胚胎暴露于间苯二酚中120 h，以评估其对甲状腺滤泡形态、视网膜发育和行为的影响。用活体荧光显微镜对甲状腺滤泡进行了分析。用组织病理学方法评估视网膜层，用明暗运动测试评估行为变化。暴露于1和30mg /L间苯二酚可导致甲状腺滤泡增生，可能表明对抑制甲状腺激素合成的代偿反应。在100 mg/L的剂量下，观察到眼睛大小缩小，多层视网膜变薄，提示继发性发育效应。此外，在暴露的胚胎中检测到运动活动增加。这些发现支持将间苯二酚归类为一种干扰物，并强调需要将组织病理学和行为终点纳入现有的经合组织测试指南，以改进对鱼类中干扰物的检测。

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引用次数: 0

Toxicity of bisphenol A alternatives: A study on bisphenol E in two generations of the freshwater snail Lymnaea stagnalis 双酚A替代品的毒性：双酚E对两代淡水蜗牛的影响

IF 4.3 2区环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY

Aquatic Toxicology

Pub Date : 2025-11-09 DOI: 10.1016/j.aquatox.2025.107641

Gaëtan Y. Tucoo, Jane E. Morthorst, Elvis Genbo Xu, Henrik Holbech

Bisphenol E (BPE), a substitute for bisphenol A (BPA), is becoming increasingly prevalent in the market and, consequently, the environment. Yet, the effects of such alternatives on aquatic organisms remain largely unknown. This study focuses on assessing the developmental toxicity of BPE in embryos (1.1 – 11,946 µg/L) from unexposed parents, as well as its reprotoxicity in adults (4.0 – 872 µg/L) of the Great Pond Snail Lymnaea stagnalis. We also examined the effects of BPE on F1 generation embryos (6.6 – 1037 µg/L) from exposed parents. Our study revealed developmental toxicity in embryos from unexposed parents from 5151 µg/L BPE, where the length, the heart rate, and hatching rate were lower than the control group. The embryo rotation was only lower at 11,946 µg/L. Malformations and delays in advancing through developmental stages were also observed. A reproduction test showed no changes in the number of laid egg masses, growth, and weight gain in snails exposed to up to 873 µg/L BPE. Only survival was affected at 187 and 873 µg/L BPE. Exposure of parents did not affect the development of embryos transferred to clean water but lowered the LOEC to 218 µg/L for F1 embryos kept exposed to BPE, compared to 5151 µg/L for exposed embryos from unexposed parents. BPE quantification using UHPLC-MS/MS revealed significant concentration variations, exceeding 20 % of the nominal concentrations, highlighting the importance of chemical analysis in chronic studies. The increased sensitivity of F1 embryos to BPE emphasizes the need for multigenerational approaches in refining ecotoxicological risk assessments of BPA alternatives.

双酚E （BPE）是双酚a （BPA）的替代品，在市场和环境中越来越普遍。然而，这些替代品对水生生物的影响在很大程度上仍然未知。本研究的重点是评估BPE在未暴露父母的胚胎（1.1 - 11,946µg/L）中的发育毒性，以及其在大池塘蜗牛成年（4.0 - 872µg/L）中的生殖毒性。我们还研究了BPE对暴露父母F1代胚胎（6.6 - 1037µg/L）的影响。我们的研究发现，未接触5151µg/L BPE的父母的胚胎发育毒性，其长度，心率和孵化率低于对照组。在11,946µg/L时，胚胎旋转率较低。还观察到发育阶段的畸形和延迟。繁殖试验显示，暴露在高达873 μ g/L BPE中的蜗牛的产蛋量、生长和体重增加没有变化。当BPE浓度为187和873µg/L时，仅影响存活。亲本暴露不影响转移到清洁水中的胚胎的发育，但暴露于BPE的F1胚胎的LOEC降低至218µg/L，而未暴露于BPE的亲本暴露胚胎的LOEC为5151µg/L。使用UHPLC-MS/MS进行BPE定量分析显示，BPE的浓度变化显著，超过了标称浓度的20%，突出了化学分析在慢性研究中的重要性。F1胚胎对BPE的敏感性增加，强调了在完善双酚a替代品的生态毒理学风险评估时需要多代方法。

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引用次数: 0

Comparative study on the reproduction toxicity of N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) to Daphnia magna based on a 21-day short-term exposure and whole-life-stage exposure and the underlying toxic mechanisms N-（1,3-二甲基丁基）-N ' -苯基-对苯二胺（6PPD）对大水蚤21天短期和终生暴露生殖毒性的比较研究及其潜在毒性机制

IF 4.3 2区环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY

Aquatic Toxicology

Pub Date : 2025-11-09 DOI: 10.1016/j.aquatox.2025.107640

Liu Yang , Xue Tang , Yongsheng Zhou , Shiniu Dai , Kexin Liu , Lina Shi , Xinli Wen

A common tire additive of N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) is frequently detected in freshwater. To date, the toxicity of 6PPD to aquatic organisms has mainly been based on partial life-cycle test results. However, it remains unclear whether this approach leads to an underestimation of the true environmental risk of 6PPD. Here, the effects of environmentally relevant or greater concentrations of 6PPD on the reproduction and growth of Daphnia magna were specifically compared between day 21 and the day all the maternal daphnia died, with the underlying toxic mechanisms of 6PPD also explored. 6PPD at environmental or near-natural water concentrations (5.68 and/or 9.20 µg/L) significantly decreased the total number of offspring and net reproductive rate after whole-life-stage exposure. However, such adverse effects were not observed on day 21, indicating that environmental levels of 6PPD exerted reproductive toxicity on D. magna, and short-term exposure may underestimate the environmental risk of 6PPD. Elevated malondialdehyde levels in the 5.68, 9.20 and 44.58 µg/L treatment groups, coupled with reactive oxygen species (ROS) emerging as the dominant contributors to the biomarker response index, indicated that ROS overproduction induced by 6PPD triggered lipid peroxidation despite antioxidant capacity was enhanced. Downregulation of the vitellogenin expression in D. magna exposed to 5.68, 9.2 and 44.58 µg/L 6PPD, likely resulting from competitive binding to ecdysteroid receptor based on molecular docking and molecular dynamics simulation, might compromise nutrient provisioning during embryogenesis. Coupled with oxidative stress, these dual mechanisms appeared to mediate 6PPD-induced reproductive toxicity.

常见的轮胎添加剂N-（1,3-二甲基丁基）-N ' -苯基-对苯二胺（6PPD）在淡水中经常被检测到。迄今为止，6PPD对水生生物的毒性主要基于部分生命周期试验结果。然而，目前尚不清楚这种方法是否会导致低估6PPD的真实环境风险。本研究特别比较了环境相关或更高浓度的6PPD对大水蚤繁殖和生长的影响，从第21天到所有母水蚤死亡的那天，并探讨了6PPD的潜在毒性机制。6PPD在环境或接近自然的水中浓度（5.68和/或9.20µg/L）显著降低了后代总数和净繁殖率。然而，在第21天没有观察到这种不良反应，这表明环境水平的6PPD对大鼠有生殖毒性，短期暴露可能低估了6PPD的环境风险。5.68、9.20和44.58µg/L处理组丙二醛水平升高，加上活性氧（ROS）成为生物标志物反应指数的主要贡献者，表明6PPD诱导的ROS过量产生引发了脂质过氧化，尽管抗氧化能力增强。暴露于5.68、9.2和44.58µg/L 6PPD下的D. magna卵黄原蛋白表达下调，可能是基于分子对接和分子动力学模拟的卵黄原蛋白与表皮甾体受体的竞争性结合，可能影响胚胎发生过程中的营养供应。再加上氧化应激，这些双重机制似乎介导了6ppd诱导的生殖毒性。

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引用次数: 0

Temperature-dependent dopaminergic disruption by chlorpromazine in the rotifer Brachionus calyciflorus: Evidence from receptor gene expression and population response 氯丙嗪对萼花臂轮虫温度依赖性多巴胺能的破坏：来自受体基因表达和群体反应的证据

IF 4.3 2区环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY

Aquatic Toxicology

Pub Date : 2025-11-04 DOI: 10.1016/j.aquatox.2025.107637

Sen Feng , Lingyun Zhu , Meng Li , Pengrui Xu , Chuhan Xu , Hairong Lian , Fan Gao , Xinfeng Cheng , Xianling Xiang

Temperature-induced amplification of drug toxicity brings about mounting ecological risks, but the effects of neuroactive substances like chlorpromazine (CPZ) on non-target aquatic invertebrates under sudden temperature shifts remain unclear. We investigated the temperature-dependent neurotoxicity of CPZ in the freshwater rotifer Brachionus calyciflorus, focusing on dopaminergic signaling. We first identified and functionally validated the dopamine receptor gene BcDopR1 in B. calyciflorus, a receptor featuring a 1371-bp open reading frame (ORF) that encodes a 456-amino acid polypeptide with seven transmembrane domains. Heterologous expression in HEK293T cells showed dopamine significantly elevated intracellular cAMP in BcDopR1-transfected cells, while CPZ dose-dependently inhibited this DA-induced cAMP response, confirming BcDopR1 as a functional D1-like dopamine receptor and CPZ as its potent antagonist. Rotifers were exposed to CPZ (0–250 μg/L) under three ecologically relevant temperatures (18, 25 and 32 °C). The peak BcDopR1 expression was observed in the control group at 25 °C, and CPZ exposure inhibited its expression in a concentration- and temperature-dependent manner. As temperature increased from 18 to 32 °C, rotifers exhibited significant reductions (p < 0.05) in several morphological traits, including lorica length, posterior lateral spine length, body size, and egg size. At the population level, the maximum population density first increased and then decreased, whereas the population growth rate increased significantly (p < 0.05). Within 0–250 μg/L CPZ, rotifers at 18 and 25 °C (except 32 °C) showed a gradual increase in lorica length and body size, whereas their egg size and maximum population density first increased then decreased. These findings highlight the susceptibility of aquatic invertebrates to neuroactive contaminants and the compounding role of thermal stress in amplifying pharmaceutical ecotoxicity. BcDopR1 emerges as a promising molecular biomarker for assessing neuroactive pharmaceutical ecological risks under climate change, and advances understanding of zooplankton adaptation to multiple environmental stressors.

温度引起的药物毒性放大带来了越来越大的生态风险，但氯丙嗪（CPZ）等神经活性物质在温度突变下对非靶水生无脊椎动物的影响尚不清楚。我们研究了CPZ在淡水轮虫萼花臂轮虫中的温度依赖性神经毒性，重点是多巴胺能信号。我们首先鉴定并功能性验证了calyciflorus中多巴胺受体基因BcDopR1，该受体具有1371 bp的开放阅读框（ORF），编码456个氨基酸的多肽，具有7个跨膜结构域。HEK293T细胞中的异源表达显示，多巴胺显著升高了BcDopR1转染细胞的胞内cAMP，而CPZ剂量依赖性地抑制了这种da诱导的cAMP反应，证实了BcDopR1是一种功能性的d1样多巴胺受体，CPZ是其有效的拮抗剂。在3种生态相关温度（18、25和32℃）下，轮虫暴露于CPZ （0 ~ 250 μg/L）。对照组在25℃时BcDopR1表达达到峰值，CPZ暴露抑制其表达呈浓度和温度依赖关系。当温度从18℃升高到32℃时，轮虫的几个形态特征，包括门廓长度、后外侧棘长、体型和卵的大小，都有显著的降低（p < 0.05）。在种群水平上，最大种群密度先升高后降低，种群增长率显著升高（p < 0.05）。在0 ~ 250 μg/L CPZ范围内，除32°C外，在18°C和25°C条件下，轮虫的轮虫体长和体型逐渐增大，卵大小和最大种群密度先增大后减小。这些发现强调了水生无脊椎动物对神经活性污染物的易感性，以及热应激在放大药物生态毒性中的复合作用。BcDopR1作为气候变化下神经活性药物生态风险评估的重要分子生物标志物，促进了对浮游动物适应多种环境胁迫的认识。

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引用次数: 0

ROS production-related phenomena and biochemical reactions of the seaweed Ulva rigida in response to the effect of environmentally relevant Bisphenol A concentrations 海藻对环境相关双酚A浓度影响下ROS产生相关现象及生化反应

IF 4.3 2区环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY

Aquatic Toxicology

Pub Date : 2025-11-04 DOI: 10.1016/j.aquatox.2025.107638

Paraskevi Malea , Maria-Markella Patronia , Marios Dermentzis , Alkistis Kevrekidou , Dimitrios Phaedon Kevrekidis

Bisphenol A (BPA) is an extensively used synthetic compound that has causes various hazardous effects on aquatic primary producers. Research on BPA impacts on marine macrophytes and especially on Ulva spp. is limited. BPA-induced oxidative stress in Ulva rigida determined even at environmentally relevant concentrations (Low Effect Concentration, LOEC: 0.3 μg L^-1, Terminal Day, TD: 7) and it was higher on 7-11D. Increases in superoxide dismutase (SOD) and ascorbate peroxidise (APX) activities on specific days and concentrations may suggest the activation of an antioxidant mechanism in response to BPA-induced oxidative stress. On 1-5D, BPA-induced oxidative stress did not sufficiently activate SOD. On 7D at 0.1 μg L^-1, SOD activity decreases the Corrected Total Cell Fluorescence (CTCF) values to the control level, whereas at 0.3 and 1 μg L^-1, both enzymes may not be able to scavenge the oxidative stress. Protein content decreases, from 7D onwards at 0.3–3 μg L^-1, which may indicate oxidative injury in these biomolecules, as the antioxidant mechanism was unable to equilibrate the oxidative stress. Oxidative stress goes hand in hand with lipid peroxidation (malondialdehyde, MDA) at 0.3 on 7D and at 0.3–3 μg L^-1 on 3D The chlorophyll (Chls), pheophytin (Phs) and carotenoid (χ+c) contents decreased on 5D at 0.1–3 μg L^-1 of BPA (LOECs: 0.1 for Chls and χ+c, 1 μg L^-1 for Phs, TD: 5). BPA toxicity, based on the thalli surface area, seemed to be BPA dose-dependent and it was more pronounced at 3D (LOEC: 0.1 μg L^-1, TD: 3). U. rigida is among the most sensitive marine macrophytes against BPA, as it can cause adverse effects on various ‘biomarkers’, even at environmental concentrations.

双酚A （BPA）是一种广泛使用的合成化合物，对水生初级生产者造成各种有害影响。关于双酚a对海洋大型植物，特别是对藻属植物的影响的研究很少。即使在环境相关浓度（低效浓度，LOEC: 0.3 μg L-1，终末日，TD: 7）下，bpa诱导的刚性木藻氧化应激也会发生，并且在7- 11d上更高。在特定的时间和浓度下，超氧化物歧化酶（SOD）和抗坏血酸过氧化物（APX）活性的增加可能表明，bpa诱导的氧化应激激活了一种抗氧化机制。在1-5D， bpa诱导的氧化应激不能充分激活SOD。当浓度为0.1 μg L-1时，第7D SOD活性使校正总细胞荧光（CTCF）值降低至对照水平，而在0.3和1 μg L-1时，两种酶均不能清除氧化应激。在0.3-3 μ L-1时，蛋白质含量从7D开始下降，这可能表明这些生物分子存在氧化损伤，因为抗氧化机制无法平衡氧化应激。当BPA浓度为0.1 - 3 μ L-1时（Chls的LOECs为0.1，χ+c的LOECs为1 μ L-1， ph的LOECs为1 μ L-1， TD为5），5D时叶绿素（Chls）、叶绿素素（Phs）和类胡萝卜素（χ+c）含量降低。基于菌体表面积的BPA毒性似乎是剂量依赖性的，并且在3D （LOEC: 0.1 μg L-1, TD: 3）时更为明显。硬藻是对双酚a最敏感的海洋大型植物之一，因为即使在环境浓度下，它也会对各种“生物标志物”产生不利影响。

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引用次数: 0