Comparative Biochemistry and Physiology C-toxicology & Pharmacology最新文献_第4页

Probiotic Enterococcus faecium NCIMB 10415 modulates florfenicol pharmacokinetics, withdrawal time, and hepatic CYP3A activity, potentially lowering antibiotic efficacy in Nile tilapia (Oreochromis niloticus) 益生菌屎肠球菌NCIMB 10415调节氟苯尼考的药代动力学、停药时间和肝脏CYP3A活性，可能降低尼罗罗非鱼（Oreochromis niloticus）的抗生素疗效。

IF 4.3 3区环境科学与生态学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Comparative Biochemistry and Physiology C-toxicology & Pharmacology

Pub Date : 2025-12-26 DOI: 10.1016/j.cbpc.2025.110438

Chi-Ming Wu , Yi-Ping Lu , Tirawat Rairat , Yu-Nan Tsai , Channarong Rodkhum , Prapansak Srisapoome , Chi-Chung Chou

Few studies have examined how probiotics affect drug efficacy in aquaculture. This study investigated impacts of Enterococcus faecium on the pharmacokinetics (PK), tissue residues, and withdrawal time (WDT) of florfenicol (FF) in Nile tilapia. Fish were orally administered E. faecium or saline at 25 °C for 10 days before receiving either a single FF dose at 10 mg/kg for the PK study or multiple doses over 5 days for the WDT evaluation. Compared to the controls, E. faecium-treated fish showed significantly reduced overall serum FF concentrations. After the single dose, the probiotic group exhibited a 32 % decrease in maximum serum concentration (C_max) and a 46 % reduction in area under the concentration-time curve (AUC), alongside a 1.8-fold increase in drug clearance (CL/F). One day after the 5-day FF treatment, the highest concentrations of FF and florfenicol amine (FFA) were found in bile, with both compounds present at higher levels in the probiotic group. E. faecium-treated fish also had a significantly lower minimum steady state serum FF concentration (2.37 ± 0.76 vs. 4.83 ± 1.06 μg/mL) and reduced total FF + FFA residues by 2.6 times in skin-on-muscle tissue, shortening WDT by one day. Furthermore, E. faecium pretreatment upregulated Cyp3A40 in the intestine and liver but did not affect Cyp1A gene, thereby maintaining CYP3A enzyme activities that would otherwise be suppressed by FF. Collectively, these results indicate that E. faecium supplements reduce FF exposure, at least in part through enhanced biliary excretion and activation of hepatic CYP3A activity, potentially requiring a higher antibiotic dosage to maintain therapeutic efficacy.

很少有研究调查益生菌如何影响水产养殖中的药物疗效。本研究探讨了粪肠球菌对氟苯尼考（FF）在尼罗罗非鱼体内的药代动力学（PK）、组织残留和停药时间（WDT）的影响。鱼在25 °C下口服粪肠杆菌或生理盐水10 天，然后在PK研究中接受10 mg/kg的单次FF剂量，或在5 天内接受多次剂量进行WDT评估。与对照组相比，粪肠杆菌处理的鱼血清中FF的总浓度显著降低。单次给药后，益生菌组的最大血清浓度（Cmax）下降了32% %，浓度-时间曲线下面积（AUC）减少了46% %，同时药物清除率（CL/F）增加了1.8倍。在FF治疗5天后的第1天，胆汁中FF和氟苯尼考胺（FFA）的浓度最高，益生菌组中这两种化合物的含量更高。粪肠杆菌处理的鱼也显著降低了最低稳态血清FF浓度（2.37 ± 0.76 vs. 4.83 ± 1.06 μg/mL），减少了皮肤和肌肉组织中FF + 总FFA残留量的2.6倍，缩短了一天的WDT。此外，粪肠杆菌预处理上调了肠道和肝脏的Cyp3A40，但不影响Cyp1A基因，从而维持了CYP3A酶的活性，否则会被FF抑制。总的来说，这些结果表明，粪肠杆菌补充剂减少FF暴露，至少部分是通过增强胆道排泄和激活肝脏CYP3A活性，可能需要更高的抗生素剂量来维持治疗效果。

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引用次数: 0

Parental exposure to phenanthrene induces thyroid disruption in zebrafish offspring 父母接触菲会导致斑马鱼后代甲状腺紊乱。

IF 4.3 3区环境科学与生态学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Comparative Biochemistry and Physiology C-toxicology & Pharmacology

Pub Date : 2025-12-22 DOI: 10.1016/j.cbpc.2025.110439

Liqiao Zhong , Fengyue Zhu , Luyin Wu , Baoshan Ma , Huijun Ru , Xinbin Duan

Polycyclic aromatic hydrocarbons (PAHs) constitute extensively studied pollutants present throughout environmental and food matrices. Phenanthrene (PHE), ranking among the most prevalent PAHs detected in food items and aquatic ecosystems, causes reproductive and developmental toxicity in zebrafish. However, the potential for PHE to transfer to zebrafish offspring and disrupt the thyroid endocrine system remains unclear. To investigate intergenerational thyroid disruption, adult zebrafish underwent PHE treatment (0, 0.85, 8.5, and 85 μg/L) for 60 days, with embryos (F1) subsequently cultured in clean water until 5 days postfertilization (dpf) and 14-dpf. Results demonstrated that PHE accumulated in zebrafish offspring through parental transmission. Parental PHE exposure induced developmental toxicity in zebrafish offspring, characterized by elevated deformation rates, diminished survival rates, and reduced body length. PHE exposure altered thyroid hormone levels and caused thyroid disruption in the F1 generation. Among F1 generation specimens (including 5 and 14-dpf larvae), L-thyroxine (T4) concentrations elevated, whereas 3,5,3′-L-triiodothyronine (T3) levels decreased. Additional investigation revealed that hypothalamic-pituitary-thyroid (HPT) axis gene transcription patterns underwent alteration following parental PHE treatment in F1 larvae. Collectively, this study established that PHE can transfer to the F1 generation from adult zebrafish, causing thyroid disruption and developmental toxicity.

多环芳烃（PAHs）是一种被广泛研究的污染物，存在于环境和食物基质中。菲（PHE）是在食品和水生生态系统中检测到的最普遍的多环芳烃之一，对斑马鱼产生生殖和发育毒性。然而，PHE转移到斑马鱼后代并破坏甲状腺内分泌系统的可能性尚不清楚。为了研究代际甲状腺破坏，研究人员对成年斑马鱼进行了60 天的PHE治疗（0、0.85、8.5和85 μg/L），随后将胚胎（F1）在清水中培养至受精后5 天（dpf）和14 dpf。结果表明，PHE通过亲代传播在斑马鱼后代中积累。亲本PHE暴露诱导斑马鱼后代发育毒性，其特征是变形率升高，存活率降低，体长缩短。PHE暴露改变了F1代的甲状腺激素水平并导致甲状腺功能紊乱。F1代标本（包括5和14-dpf幼虫）中，l -甲状腺素（T4）浓度升高，而3,5,3′- l -三碘甲状腺原氨酸（T3）水平降低。进一步的研究表明，在亲本PHE处理后，F1幼虫的下丘脑-垂体-甲状腺（HPT）轴基因转录模式发生了改变。总的来说，本研究确定PHE可以从成年斑马鱼转移到F1代，导致甲状腺紊乱和发育毒性。

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引用次数: 0

Acute heat stress reprograms the circadian–inflammatory–metabolic axis in Lasiopodomys brandtii 急性热应激重编程布氏Lasiopodomys brandtii的生理-炎症-代谢轴。

IF 4.3 3区环境科学与生态学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Comparative Biochemistry and Physiology C-toxicology & Pharmacology

Pub Date : 2025-12-22 DOI: 10.1016/j.cbpc.2025.110435

Xi-Zhi Wang , Ying Li , Chen-Zhu Wang , Zhen-Shan Wang , Xue-Ying Zhang

Ongoing climate warming, particularly intensifying heatwaves, imposes substantial physiological stress on small mammals. Although heat-induced responses have been extensively studied in laboratory models, little is known about how wild small mammals respond to acute thermal stress. To address this gap, we investigated the physiological responses of Brandt's voles (Lasiopodomys brandtii), a diurnal herbivorous rodent native to typical steppe regions of Inner Mongolia, under acute heat exposure (36 °C). Heat-treated voles showed a 1.4 °C rise in core body temperature and a 37 % reduction in metabolic rate, accompanied by a phase advance in the circadian rhythm and the emergence of an 11.8 h ultradian rhythm. Gene expression profiling revealed upregulation of circadian repressors (Per2 and Cry1) and pro-inflammatory genes (Nfκb or Il1α) in the hypothalamus, liver and brown adipose tissue (BAT), and tissue-specific alterations in thermogenic regulators (Pgc1α). Concurrent with these changes, serum TNF-α levels elevated, IL-6 reduced, and thyroxine (T4) increased, while serum T3 remained stable. Correlation analyses showed that Per2 and Cry1 expression in the liver, but not in the hypothalamus or BAT, were positively associated with serum TNF-α, whereas in the hypothalamus and BAT, clock genes were primarily linked to local inflammatory markers such as Nfκb and Il1α. Network modeling further identified Per2 and Bmal1 as central hub genes across tissues, orchestrating regulatory interactions with both inflammatory and metabolic genes. These findings suggest that heat-induced circadian disruption involves tissue-specific interactions between clock genes and immune-metabolic signals, underscoring the circadian system's key role in coordinating adaptive responses to acute thermal stress.

持续的气候变暖，特别是不断加剧的热浪，给小型哺乳动物带来了巨大的生理压力。尽管热诱导反应已经在实验室模型中进行了广泛的研究，但人们对野生小型哺乳动物如何对急性热应激作出反应知之甚少。为了解决这一空白，我们研究了勃兰特田鼠（Lasiopodomys brandtii）在急性热暴露（36 °C）下的生理反应。勃兰特田鼠是一种原产于典型草原地区的日间食草啮齿动物。经过热处理的田鼠的核心体温升高了1.4 °C，代谢率降低了37 %，同时它们的昼夜节律提前了一个阶段，并出现了11.8 小时的超昼夜节律。基因表达谱显示，下丘脑、肝脏和棕色脂肪组织（BAT）的昼夜节律抑制因子（Per2和Cry1）和促炎基因（Nfκb或Il1α）上调，产热调节因子（Pgc1α）的组织特异性改变。与此同时，血清TNF-α水平升高，IL-6降低，甲状腺素（T4）升高，而血清T3保持稳定。相关分析显示，Per2和Cry1在肝脏中的表达与血清TNF-α呈正相关，而在下丘脑和BAT中没有，而在下丘脑和BAT中，时钟基因主要与局部炎症标志物如Nfκb和il -α相关。网络模型进一步确定Per2和Bmal1是跨组织的中心枢纽基因，与炎症和代谢基因协调调节相互作用。这些发现表明，热诱导的昼夜节律紊乱涉及生物钟基因和免疫代谢信号之间的组织特异性相互作用，强调了昼夜节律系统在协调急性热应激适应性反应中的关键作用。

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引用次数: 0

Intergenerational effects of parental dimefluthrin and microcystins co-exposure on zebrafish: Impaired embryonic and larval development 父母二甲基菊酯和微囊藻毒素共同暴露对斑马鱼的代际影响：胚胎和幼虫发育受损。

IF 4.3 3区环境科学与生态学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Comparative Biochemistry and Physiology C-toxicology & Pharmacology

Pub Date : 2025-12-20 DOI: 10.1016/j.cbpc.2025.110437

Yinhui Xu , Bo Gao , Rongkai Bao , Yafang Shi , Wenhua Li , Peng Xiao

Dimefluthrin (DIM), a widely used pyrethroid insecticide, and microcystin-LR (MC-LR), a potent cyanotoxin produced by harmful algal blooms, are both frequently detected in aquatic environments. However, the potential combined effects of these two contaminants, particularly regarding intergenerational toxicity, remain largely unexplored. In this study, we aimed to evaluate the intergenerational effects of chronic parental co-exposure to DIM and MC-LR in zebrafish. Adult zebrafish were exposed to DIM and MC-LR, alone or in combination, for 160 days. A panel of phenotypic, histological, biochemical, and transcriptomic analyses were conducted in both adults and their F1 offspring. Chronic co-exposure resulted in ovarian and hepatic tissue damage and reduced spawning rates in adult zebrafish. In the F1 generation, significant developmental abnormalities were observed, including reduced heart rate, spinal curvature, and impaired swim bladder inflation. These phenotypic defects were accompanied by significant downregulation of the mesothelial markers anxa5b and hprt1l, both of which contribute to swim bladder development in F1 larvae. Transcriptomic analysis revealed enrichment of ferroptosis-related pathways in maternal ovaries and both ferroptosis and necroptosis pathways in F1 larvae. Furthermore, mouse double minute 2 homolog (MDM2), fatty acid synthase (FASN), and farnesoid X receptor (FXR) were identified through molecular docking as potential DIM-interacting targets implicated in the regulation of ferroptosis. These findings provide new insights into the multigenerational risks posed by co-exposure to environmental pesticides and cyanotoxins, and emphasize the importance of incorporating intergenerational effects into water quality guidelines and chemical management strategies.

二甲基氟菊酯（DIM）是一种广泛使用的拟除虫菊酯杀虫剂，微囊藻毒素（MC-LR）是一种由有害藻华产生的强效氰毒素，两者都经常在水生环境中被检测到。然而，这两种污染物的潜在综合影响，特别是代际毒性，在很大程度上仍未得到探索。在这项研究中，我们旨在评估慢性父母共同暴露于DIM和MC-LR对斑马鱼的代际影响。成年斑马鱼单独或联合暴露于DIM和MC-LR中160 天。一组表型，组织学，生化和转录组分析进行了成人和他们的F1后代。慢性共暴露导致成年斑马鱼卵巢和肝脏组织损伤并降低产卵率。在F1代中，观察到明显的发育异常，包括心率降低、脊柱弯曲和鱼鳔膨胀受损。这些表型缺陷伴随着间皮标记物anxa5b和hprt1l的显著下调，这两个标记物都有助于F1幼虫的鱼鳔发育。转录组学分析显示，在母体卵巢中，铁下垂相关通路丰富，在F1幼虫中，铁下垂和坏死性下垂通路都丰富。此外，通过分子对接，小鼠双分钟2同源物（MDM2）、脂肪酸合成酶（FASN）和法氏体X受体（FXR）被确定为参与铁死亡调节的潜在dim相互作用靶点。这些研究结果为共同暴露于环境农药和蓝藻毒素所带来的多代风险提供了新的见解，并强调了将代际影响纳入水质准则和化学品管理战略的重要性。

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引用次数: 0

Synergistic effects of high temperature and hypoxia on energy metabolism and physiological homeostasis in the Chinese mitten crab (Eriocheir sinensis) 高温和缺氧对中华绒螯蟹能量代谢和生理稳态的协同作用

IF 4.3 3区环境科学与生态学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Comparative Biochemistry and Physiology C-toxicology & Pharmacology

Pub Date : 2025-12-16 DOI: 10.1016/j.cbpc.2025.110436

Cong Zhang , Dunqian Deng , Huixia Feng , Su Jiang , Zihao Song , Kai Zhang , Longlong Fu , Shaowu Yin

High temperature and hypoxia are critical environmental stressors affecting the intensive aquaculture of the Chinese mitten crab (Eriocheir sinensis). This study aimed to investigate the differential physiological response mechanisms of juvenile crabs under single stress and combined stress. The results revealed that combined high-temperature and hypoxia stress exerted a significant synergistic negative effect on juvenile crabs compared to single stressors. Under combined stress, mitochondrial structural damage is observed in gill tissues, accompanied by markedly reduced activities of cytochrome c oxidase and cytochrome c, indicating impairment of the aerobic respiratory pathway. In response, the hepatopancreas undergoes reconstruction of energy metabolism patterns, characterized by a significant decrease in glycogen content, along with elevated levels of glucose, pyruvate, and lactate in the hemolymph. In addition, the activities of hexokinase and pyruvate kinase in the hepatopancreas increased, while succinate dehydrogenase activity decreased. Concurrently, the function of the antioxidant system is dysregulated, with decreases in total antioxidant capacity and glutathione levels, and the expression of antioxidant-related genes shows a similar trend. In addition, the expression levels of immune- and apoptosis-related genes were significantly up-regulated. These results indicate that combined stress leads to systemic energy metabolism disorder, exacerbated oxidative stress, pro-inflammatory response and apoptosis, and functional organ damage. The results underscore that combined environmental stressors can induce nonlinear and more severe physiological damage.

高温和缺氧是影响中华绒螯蟹集约化养殖的重要环境胁迫因素。本研究旨在探讨蟹幼鱼在单一胁迫和复合胁迫下的生理反应机制差异。结果表明，与单一应激源相比，高温低氧复合应激对蟹幼鱼具有显著的协同负作用。在联合应激下，鳃组织线粒体结构损伤，细胞色素c氧化酶和细胞色素c活性明显降低，表明有氧呼吸通路受损。作为回应，肝胰脏经历能量代谢模式的重建，其特征是糖原含量显著降低，同时血淋巴中葡萄糖、丙酮酸和乳酸水平升高。肝胰脏己糖激酶和丙酮酸激酶活性升高，琥珀酸脱氢酶活性降低。同时，抗氧化系统功能失调，总抗氧化能力和谷胱甘肽水平下降，抗氧化相关基因表达也呈现类似趋势。此外，免疫和凋亡相关基因的表达水平显著上调。上述结果提示，复合应激导致全身能量代谢紊乱，氧化应激加剧，促炎反应和细胞凋亡加剧，功能器官受损。结果表明，复合环境应激可引起非线性且更为严重的生理损伤。

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引用次数: 0

2-Hydroxyanthraquinone exposure causes the damage of cerebrovascular and blood brain barrier in zebrafish via inducing inflammation and downregulation of the Wnt/β-catenin signaling pathway 2-羟基蒽醌暴露通过诱导炎症和下调Wnt/β-catenin信号通路导致斑马鱼脑血管和血脑屏障的损伤。

IF 4.3 3区环境科学与生态学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Comparative Biochemistry and Physiology C-toxicology & Pharmacology

Pub Date : 2025-12-10 DOI: 10.1016/j.cbpc.2025.110432

Huimin Li , Ziang Wang , Suwei He , Minghui Zhong , Xichen Wang , Weitao Hu , Jingrong Tang , Zhonghao Xiao , Xiaowen Shi , Zigang Cao

2-Hydroxyanthraquinone (2-hATQ), a photooxidation product of anthracene (ANT) within polycyclic aromatic hydrocarbons (PAHs), poses significant risks to ecological safety and human health. ANT is listed as a priority pollutant by the U.S. Environmental Protection Agency (EPA) due to its persistence and resistance to degradation in the environment. Consequently, 2-hATQ, inheriting these characteristics from its parent compound, is ubiquitously present in the environment and exhibits greater toxicity than ANT itself. However, research on its toxicological effects, particularly concerning cerebrovascular toxicity, remains limited. In this study, acute exposure of zebrafish embryos to various concentrations of 2-hATQ resulted in significant cerebrovascular developmental abnormalities, manifested as reduced total vascular area and decreased vessel number in the brain. Moreover, the number of brain microglia, reactive oxygen species (ROS) levels, and apoptotic cell counts were markedly increased. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed that 2-hATQ disrupts zebrafish cerebrovascular and blood-brain barrier development by upregulating pro-inflammatory cytokines (il1β, tnf-α, nf-κb, il6) and inhibiting the Wnt/β-catenin signaling pathway (lef1, β-catenin, dkk1, wif1). The co-administration of dexamethasone or BML-284 effectively rescued the cerebrovascular damage. Furthermore, behavioral analysis demonstrated that exposed zebrafish larvae exhibited reduced locomotor activity and anxiety-like states. This study reveals for the first time the adverse effects of 2-hATQ exposure on brain vascular development in aquatic organisms, suggesting that 2-hATQ and its ANT-related derivatives may be potential risk factors for cerebrovascular diseases. Our findings reveal, for the first time, that 2-hATQ impairs cerebrovascular and BBB development through concurrent induction of inflammation and suppression of the Wnt/β-catenin pathway, identifying these as critical mechanistic events in its toxicity.

2-羟基蒽醌（2-hATQ）是多环芳烃（PAHs）中蒽（ANT）的光氧化产物，对生态安全和人体健康构成重大威胁。由于其在环境中的持久性和抗降解性，ANT被美国环境保护署（EPA）列为优先污染物。因此，2-hATQ继承了母体化合物的这些特征，在环境中无处不在，并表现出比ANT本身更大的毒性。然而，对其毒理学效应，特别是脑血管毒性的研究仍然有限。在本研究中，斑马鱼胚胎急性暴露于不同浓度的2-hATQ中，导致明显的脑血管发育异常，表现为大脑血管总面积减少和血管数量减少。此外，脑小胶质细胞数量、活性氧（ROS）水平和凋亡细胞计数明显增加。定量实时聚合酶链反应（qRT-PCR）分析显示，2-hATQ通过上调促炎细胞因子（il - 1β、tnf-α、nf-κb、il - 6）和抑制Wnt/β-catenin信号通路（lef1、β-catenin、dkk1、wif1），破坏斑马鱼脑血管和血脑屏障的发育。联合应用地塞米松或BML-284可有效挽救脑血管损伤。此外，行为分析表明，暴露的斑马鱼幼虫表现出运动活动减少和焦虑样状态。本研究首次揭示了2-hATQ暴露对水生生物脑血管发育的不良影响，提示2-hATQ及其ant相关衍生物可能是脑血管疾病的潜在危险因素。我们的研究结果首次揭示，2-hATQ通过同时诱导炎症和抑制Wnt/β-catenin通路来损害脑血管和血脑屏障的发育，并确定这些是其毒性的关键机制事件。

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引用次数: 0

O-phenylphenol induces cardiac injury by regulating cardiac progenitor cells in zebrafish (Danio rerio) 邻苯酚通过调节斑马鱼心脏祖细胞诱导心脏损伤。

IF 4.3 3区环境科学与生态学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Comparative Biochemistry and Physiology C-toxicology & Pharmacology

Pub Date : 2025-12-07 DOI: 10.1016/j.cbpc.2025.110429

Xiaomei Chen , Yong Huang , Zekun Li , Wei Yuan , Jun Guo , Yuyang Peng , Runhao Zhu , Huiqiang Lu , Jian Yang

O-phenylphenol (OPP) is a widely used environmental contaminant, but its potential toxic effects on vertebrate cardiovascular development remain poorly understood. This study systematically evaluated OPP's developmental and cardiotoxic effects using zebrafish models, combining embryological exposure (0–9 mg/L, 5–72 h post-fertilization) with adult chronic exposure (0–4 mg/L, 30 days). Embryonic assessments combined morphological analysis, in situ hybridization, transcriptomics, and molecular pathway characterization, while adult chronic exposure studies focused on histological and functional cardiac evaluations. Our findings demonstrated that embryonic OPP exposure induced dose-dependent developmental toxicity, including reduced body length, yolk sac expansion, and cardiac malformations ranging from mild (heart linearization) to severe (cardia bifida). In situ hybridization confirmed that cardia bifida hearts possessed independent atrial and ventricular chambers. Mechanistically, OPP inhibited cardiac progenitor cell migration and suppressed the expression of migration-related genes (gata4, snai1a). OPP exposure also inhibited ATPase activity, resulting in impaired cardiac function, as demonstrated by reduced cardiac output and decreased heart rate. Furthermore, transcriptomic analysis revealed concomitant dysregulation of calcium signaling and cardiac muscle contraction pathways. Adult exposure induced myocardial fiber dissolution and cardiomyocyte nuclear enlargement. These findings demonstrate that OPP compromises cardiac development through progenitor cell migration defects and impairs cardiac function via ATPase inhibition and calcium signaling disruption. This study provides valuable insights into the potential cardiotoxic risks associated with environmental toxins.

邻苯酚（OPP）是一种广泛使用的环境污染物，但其对脊椎动物心血管发育的潜在毒性作用尚不清楚。本研究利用斑马鱼模型，结合胚胎暴露（0-9 mg/L，受精后5-72 小时）和成年慢性暴露（0-4 mg/L， 30 天），系统评估了OPP的发育和心脏毒性作用。胚胎评估结合形态学分析、原位杂交、转录组学和分子途径表征，而成人慢性暴露研究侧重于组织学和心脏功能评估。我们的研究结果表明，胚胎暴露于OPP诱导了剂量依赖性的发育毒性，包括体长缩短、卵黄囊扩张和从轻微（心脏线性化）到严重（贲门裂）的心脏畸形。原位杂交证实裂心具有独立的心房和心室。在机制上，OPP抑制心脏祖细胞迁移并抑制迁移相关基因的表达（gata4, snai1a）。OPP暴露也会抑制atp酶活性，导致心功能受损，如心输出量减少和心率下降所证明的那样。此外，转录组学分析揭示了钙信号和心肌收缩途径的失调。成人暴露引起心肌纤维溶解和心肌细胞核增大。这些发现表明，OPP通过祖细胞迁移缺陷损害心脏发育，并通过atp酶抑制和钙信号干扰损害心脏功能。这项研究为与环境毒素相关的潜在心脏毒性风险提供了有价值的见解。

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引用次数: 0

Phosphorus-potassium fertilizer exposure induces oxidative stress and riboflavin metabolism disruption in juvenile turbot (Scophthalmus maximus) 磷钾肥暴露诱导大菱鲆幼鱼氧化应激和核黄素代谢紊乱。

IF 4.3 3区环境科学与生态学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Comparative Biochemistry and Physiology C-toxicology & Pharmacology

Pub Date : 2025-12-06 DOI: 10.1016/j.cbpc.2025.110430

Ying Tao , Xin Li , Lele Wu , Ting Qi , Xinlu Yue , Xian Li

Intensive agriculture's excessive fertilizer use significantly contributes to coastal nutrient pollution. While phosphorus's ecological impacts are recognized, the toxicity of combined phosphorus nutrients on marine life remains unclear. This study examined phosphorus-potassium fertilizer's (P-K fertilizer) effects on juvenile turbot (Scophthalmus maximus) via a 96-hour acute exposure experiment. Exposure solutions were prepared at environmentally relevant concentrations, resulting in elevated seawater phosphorus and potassium levels by 117.25 mg/L and 152.94 mg/L, respectively. Compound fertilizer aggravated multi-tissue damage, such as gill epithelial cell proliferation. Untargeted metabolomics identified that P-K fertilizer disrupts riboflavin metabolism, leading to reduced riboflavin levels. This deficiency impaired the production of flavin mononucleotide and flavin adenine dinucleotide. Meanwhile, excess potassium ions triggered Na⁺/K⁺ ATPase pump and gene of the renal outer medullary K⁺ channel to maintain ionic balance. Following riboflavin metabolism disruption, juvenile turbot exhibited impaired antioxidant capacity, with significantly decreased activities of glutathione peroxidase (by 54.5 %) and superoxide dismutase (by 12.6 %), a significant increase in catalase activity, obvious accumulation of malondialdehyde, and a reduction in total antioxidant capacity. The changes in related gene expression measured by real-time qPCR were consistent with the observed alterations in enzyme activities. Overall, compared to exposure to PO₄³⁻-P alone, the combined P-K fertilizer exposure resulted in more severe disruption of riboflavin metabolism and exacerbated oxidative damage in marine fish, indicating that K⁺ potentiated the adverse effects through synergistic interactions. This work provides critical insights for managing nutrient pollution in marine ecosystems and safeguarding coastal biodiversity and ecosystem services.

集约化农业的过度施肥是造成沿海养分污染的重要原因。虽然磷的生态影响已被认识到，但磷营养物对海洋生物的毒性仍不清楚。通过96小时急性暴露试验，研究了磷钾肥对大菱鲆（Scophthalmus maximus）幼鱼的影响。在与环境相关的浓度下制备暴露溶液，导致海水中磷和钾含量分别升高117.25 mg/L和152.94 mg/L。复合肥加重了鳃上皮细胞增殖等多组织损伤。非靶向代谢组学发现，磷钾肥破坏核黄素代谢，导致核黄素水平降低。这种缺陷损害了黄素单核苷酸和黄素腺嘌呤二核苷酸的产生。同时，过量的钾离子触发Na+/K+ atp酶泵和肾外髓K+通道基因维持离子平衡。核黄素代谢紊乱后，大菱鲆幼鱼抗氧化能力受损，谷胱甘肽过氧化物酶和超氧化物歧化酶活性显著降低（降低54.5 %），超氧化物歧化酶活性显著降低（降低12.6 %），过氧化氢酶活性显著升高，丙二醛积累明显，总抗氧化能力降低。实时荧光定量pcr检测到的相关基因表达变化与观察到的酶活性变化一致。总体而言，与PO43- P单独暴露相比，磷钾肥复合暴露导致海洋鱼类核黄素代谢受到更严重的破坏，并加剧了氧化损伤，这表明K+通过协同作用增强了不利影响。这项工作为管理海洋生态系统中的营养污染和保护沿海生物多样性和生态系统服务提供了重要见解。

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引用次数: 0

Toxicological and metabolic responses of Chironomus tepperi larvae to acute and chronic PFOS exposure 急性和慢性全氟辛烷磺酸暴露对麻鼠幼虫的毒理学和代谢反应。

IF 4.3 3区环境科学与生态学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Comparative Biochemistry and Physiology C-toxicology & Pharmacology

Pub Date : 2025-12-06 DOI: 10.1016/j.cbpc.2025.110428

Anu Kumar , Thao V. Nguyen , Bhanu Nidumolu , Natoiya Lloyd , Peter Goonan

The present study investigated the acute and chronic toxicity, bioaccumulation potential, and metabolic disruptions induced by perfluorooctane sulfonate (PFOS) in larvae of the freshwater Chironomus tepperi using a multidisciplinary approach integrating apical endpoints with targeted and untargeted metabolomics. Acute toxicity tests revealed a 48-h EC50 of 1.13 mg/L (95 % CI:1.14 to 1.51 mg/L) and EC10 of 0.40 mg/L, while 7-day chronic exposures resulted in an EC50 of 58.01 μg/L (95 % CI: 30.33 to 74.53 μg/L) and EC10 of 0.31 μg/L. Larval growth after 7 days of exposure, measured as length, was significantly affected at 50 μg/L, highlighting its sensitivity to PFOS exposure. Bioaccumulation of PFOS in midge larvae increased linearly with exposure concentrations, reaching 560 ± 212 μg/kg at 50 μg/L. Targeted amino acid profiling identified 15 significantly altered amino acids, including increased levels of glutamine and lysine, suggesting disrupted protein metabolism. Untargeted GC–MS metabolomics revealed 37 significantly affected metabolites and 24 enriched metabolic pathways, including those involved in amino acid biosynthesis, energy metabolism (glycolysis and pyruvate metabolism), nitrogen elimination, and redox balance (glutathione and taurine metabolism). Notably, this study provides the first integrated assessment of PFOS-induced metabolic perturbations in C. tepperi, linking molecular-level responses with organismal toxicity outcomes and identifying novel biochemical pathways affected even at environmentally relevant concentrations. The integration of metabolomics data with conventional toxicity endpoints provides mechanistic insight into PFOS-induced effects and supports the use of C. tepperi in environmental monitoring and risk assessment frameworks for PFAS.

本研究采用多学科方法，将尖端终点与靶向和非靶向代谢组学相结合，研究了全氟辛烷磺酸（PFOS）对淡水Chironomus teperi幼虫的急性和慢性毒性、生物蓄能潜力和代谢破坏。急性毒性试验显示，48小时EC50为1.13 mg/L(95 % CI:1.14 ~ 1.51 mg/L)， EC10为0.40 mg/L，而7天慢性暴露的EC50为58.01 μg/L(95 % CI: 30.33 ~ 74.53 μg/L)， EC10为0.31 μg/L。50 μg/L对暴露7 天后的幼虫生长有显著影响，说明其对全氟辛烷磺酸的敏感性。全氟辛烷磺酸在蠓幼虫体内的生物累积量随暴露浓度的增加呈线性增加，在50 μg/L时达到560 ± 212 μg/kg。靶向氨基酸分析鉴定出15种显著改变的氨基酸，包括谷氨酰胺和赖氨酸水平升高，表明蛋白质代谢受到干扰。非靶向GC-MS代谢组学显示，37种代谢物受到显著影响，24种代谢途径富集，包括氨基酸生物合成、能量代谢（糖酵解和丙酮酸代谢）、氮消除和氧化还原平衡（谷胱甘肽和牛磺酸代谢）。值得注意的是，本研究首次提供了对pfos诱导的tepperi代谢扰动的综合评估，将分子水平的反应与有机毒性结果联系起来，并确定了即使在环境相关浓度下也会受到影响的新的生化途径。代谢组学数据与传统毒性终点的整合提供了pfos诱导效应的机制洞察，并支持将C. tepperi用于PFAS的环境监测和风险评估框架。

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引用次数: 0

Immunotoxicity and mechanism analysis of zebrafish embryos exposure to benzothiazole and its derivatives 苯并噻唑及其衍生物对斑马鱼胚胎的免疫毒性及机制分析。

IF 4.3 3区环境科学与生态学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Comparative Biochemistry and Physiology C-toxicology & Pharmacology

Pub Date : 2025-12-05 DOI: 10.1016/j.cbpc.2025.110427

Wan-Ting Huang , Run-Fan Wu , Zhong-Qian Xuan , Jia-Qi Wu , Ming-Fang He

Benzothiazole derivatives (BTHs), including benzothiazole (BTH), 2-hydroxybenzothiazole (OBT), 2-aminobenzothiazole (NTH), and 2-(methylthio)benzothiazole (MTBT), pose significant exposure risks to organisms. Despite their recognized toxicity, the immunotoxic effects of BTHs remain poorly understood. This study systematically evaluated the immunotoxicity of four BTHs (BTH: 50 μM, 100 μM, and 200 μM; OBT: 50 μM, 100 μM, and 200 μM; NTH: 25 μM, 50 μM, and 100 μM; and MTBT: 3.125 μM, 6.25 μM, and 12.5 μM) in zebrafish embryos, including developmental toxicity, innate immune cell responses, oxidative stress levels, and bacterial challenge experiments were conducted to determine the impact of BTHs on pathogen resistance. RNA-seq and qRT-PCR assay were used to determine the mechanisms underlying BTHs-induced immunotoxicity. Results showed that BTH, OBT, NTH, and MTBT exposure caused developmental abnormalities, reduced macrophage and neutrophils numbers, and induced oxidative stress, including superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), and reactive oxygen species (ROS). Bacterial challenge assay revealed that BTH, OBT, NTH, and MTBT significantly impaired zebrafish resistance to bacterial infection. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified key differentially expressed genes (DEGs) in the TLR/NLR-NF-κB signaling pathway following BTH-exposure, which were further validated by qRT-PCR. In summary, BTHs not only exhibit developmental toxicity but also induce immunotoxicity by disrupting the Toll-like Receptors - Nucleotide-binding Oligomerization Domain-like Receptors - Nuclear Factor kappa-B (TLR/NLR-NF-κB) signaling pathway. These findings provide critical insights into the ecological risks of BTHs exposure in aquatic environments.

苯并噻唑衍生物（BTHs），包括苯并噻唑（BTH）、2-羟基苯并噻唑（OBT）、2-氨基苯并噻唑（NTH）和2-（甲基硫）苯并噻唑（MTBT），对生物体具有显著的暴露风险。尽管BTHs具有公认的毒性，但其免疫毒性作用仍知之甚少。本研究系统的免疫毒性评价四个蓝芽(蓝芽:50 μM, 100 μM,和200年 μM, OBT: 50 μM, 100 μM,和200年 μM, n: 25 μM, 50μM,和100年 μM, MTBT: 3.125 μM, 6.25μM和12.5 μM)在斑马鱼胚胎,包括发育毒性,先天免疫细胞反应、氧化应激水平,和细菌挑战实验来确定蓝芽在病原体耐药性的影响。采用RNA-seq和qRT-PCR检测bths诱导免疫毒性的机制。结果表明，BTH、OBT、NTH和MTBT暴露导致发育异常，巨噬细胞和中性粒细胞数量减少，并诱导氧化应激，包括超氧化物歧化酶（SOD）、丙二醛（MDA）、过氧化氢酶（CAT）和活性氧（ROS）。细菌攻击试验显示，BTH、OBT、NTH和MTBT显著削弱了斑马鱼对细菌感染的抵抗力。京都基因与基因组百科（KEGG）分析鉴定出bth暴露后TLR/NLR-NF-κB信号通路中的关键差异表达基因（DEGs），并通过qRT-PCR进一步验证。综上所述，BTHs不仅表现出发育毒性，而且通过破坏toll样受体-核苷酸结合寡聚结构域样受体-核因子κ b （TLR/NLR-NF-κ b）信号通路诱导免疫毒性。这些发现为水生环境中接触BTHs的生态风险提供了重要见解。

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引用次数: 0