Pub Date : 2026-01-06DOI: 10.1016/j.cbpc.2025.110442
Tingting Liu , Jia Wang , Minghao Yu , Yining Li , Huan Lin , Dan Deng , Xiaolu Shi , Xiaoping Xiao
This review systematically examines the mechanisms through which multiple environmental pollutants-including microplastics, heavy metals, atmospheric particulates, pesticide residues, water eutrophication, and artificial light at night-synergistically exacerbate the transmission risk of mosquito-borne diseases. A conceptual framework of the “pollution - resistance - transmission” vicious cycle is proposed, illustrating how pollutants not only directly impair mosquito physiology and drive the evolution of insecticide resistance but also systematically enhance pathogen transmission efficiency by reshaping vector-host-environment interactions, altering host behavior, compromising immune function, and extending mosquito activity periods. Interactions among pollutants, such as the role of microplastics as “Trojan horses” that carry other contaminants, further amplify ecological and health risks through combined exposure. The review also highlights species-specific and context-dependent variations in responses, identifies key research bottlenecks, and proposes multi-level intervention strategies integrating technological innovation with systematic governance-encompassing source control, process interruption, and ecological restoration-to provide a scientific basis for harmonizing public health and ecological security.
{"title":"Review: Synergistic effects of environmental pollutants: Multiple stressors driving the transmission of vector-borne diseases and the vicious cycle","authors":"Tingting Liu , Jia Wang , Minghao Yu , Yining Li , Huan Lin , Dan Deng , Xiaolu Shi , Xiaoping Xiao","doi":"10.1016/j.cbpc.2025.110442","DOIUrl":"10.1016/j.cbpc.2025.110442","url":null,"abstract":"<div><div>This review systematically examines the mechanisms through which multiple environmental pollutants-including microplastics, heavy metals, atmospheric particulates, pesticide residues, water eutrophication, and artificial light at night-synergistically exacerbate the transmission risk of mosquito-borne diseases. A conceptual framework of the “pollution - resistance - transmission” vicious cycle is proposed, illustrating how pollutants not only directly impair mosquito physiology and drive the evolution of insecticide resistance but also systematically enhance pathogen transmission efficiency by reshaping vector-host-environment interactions, altering host behavior, compromising immune function, and extending mosquito activity periods. Interactions among pollutants, such as the role of microplastics as “Trojan horses” that carry other contaminants, further amplify ecological and health risks through combined exposure. The review also highlights species-specific and context-dependent variations in responses, identifies key research bottlenecks, and proposes multi-level intervention strategies integrating technological innovation with systematic governance-encompassing source control, process interruption, and ecological restoration-to provide a scientific basis for harmonizing public health and ecological security.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"302 ","pages":"Article 110442"},"PeriodicalIF":4.3,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932575","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 : 2026-01-05DOI: 10.1016/j.cbpc.2026.110450
Asare Derrick , Yudong Zheng , Bissih Fred , Agyenim Godfred Boateng , Hongming Wang , Peter Mrope , Samuel Azupio , Shuang Zhang
The accumulation of heavy metals in aquatic environments poses critical threats to aquaculture, with iron (Fe) being one of the most prevalent contaminants from industrial and agricultural effluents. This study evaluated the acute toxicity and mechanistic impacts of ferrous sulfate (FeSO₄) on the Pacific white shrimp (Litopenaeus vannamei). Acute toxicity tests established the 96-h median lethal concentration (LC₅₀) of Fe at 2.52 mg/L, determined across exposure intervals of 0, 24, 48, 72, and 96-h at nominal concentrations ranging from 0.2, 1.0, 5.0, 25.0, 125.0, and 625.0 mg/L. No mortality occurred in control shrimp, whereas mortality increased progressively with both concentration and duration of FeSO₄ exposure. FeSO₄ exposure caused significant Fe accumulation in hepatopancreas and muscle, accompanied by elevated reactive oxygen species and malondialdehyde, and suppression of key antioxidant and immune enzymes; superoxide dismutase (SOD), catalase (CAT), and lysozyme (LZM). Transcriptional analysis revealed strong upregulation of stress proteins (HSP70, HSP90, GSH-Px), apoptotic regulators (caspase-3, p53), and immune effectors (metallothionein), whereas ferritin expression decreased, indicating disruption of Fe homeostasis. Microbiota sequencing demonstrated pronounced dysbiosis: control shrimp maintained balanced commensal taxa, while Fe-exposed groups were enriched in stress-tolerant and opportunistic genera such as Shewanella and Vibrio. Functional prediction (Tax4Fun) indicated that Fe exposure enhanced xenobiotic biodegradation, immune diseases, and cell-death–related pathways, while functions associated with energy, amino-acid and carbohydrate metabolism, and nervous system were comparatively downregulated. Collectively, FeSO₄ exposure impaired antioxidant defences, triggered apoptosis, and induced intestinal dysbiosis, with implications for aquaculture health management and environmental risk assessment.
{"title":"Effects of short-term exposure to ferrous sulfate on bioaccumulation, oxidative stress biomarkers, immunity, and intestinal microbiota in Litopenaeus vannamei","authors":"Asare Derrick , Yudong Zheng , Bissih Fred , Agyenim Godfred Boateng , Hongming Wang , Peter Mrope , Samuel Azupio , Shuang Zhang","doi":"10.1016/j.cbpc.2026.110450","DOIUrl":"10.1016/j.cbpc.2026.110450","url":null,"abstract":"<div><div>The accumulation of heavy metals in aquatic environments poses critical threats to aquaculture, with iron (Fe) being one of the most prevalent contaminants from industrial and agricultural effluents. This study evaluated the acute toxicity and mechanistic impacts of ferrous sulfate (FeSO₄) on the Pacific white shrimp (<em>Litopenaeus vannamei</em>). Acute toxicity tests established the 96-h median lethal concentration (LC₅₀) of Fe at 2.52 mg/L, determined across exposure intervals of 0, 24, 48, 72, and 96-h at nominal concentrations ranging from 0.2, 1.0, 5.0, 25.0, 125.0, and 625.0 mg/L. No mortality occurred in control shrimp, whereas mortality increased progressively with both concentration and duration of FeSO₄ exposure. FeSO₄ exposure caused significant Fe accumulation in hepatopancreas and muscle, accompanied by elevated reactive oxygen species and malondialdehyde, and suppression of key antioxidant and immune enzymes; superoxide dismutase (SOD), catalase (CAT), and lysozyme (LZM). Transcriptional analysis revealed strong upregulation of stress proteins (<em>HSP70, HSP90, GSH-Px</em>), apoptotic regulators (<em>caspase-3, p53</em>), and immune effectors (<em>metallothionein</em>), whereas <em>ferritin</em> expression decreased, indicating disruption of Fe homeostasis. Microbiota sequencing demonstrated pronounced dysbiosis: control shrimp maintained balanced commensal taxa, while Fe-exposed groups were enriched in stress-tolerant and opportunistic genera such as <em>Shewanella</em> and <em>Vibrio</em>. Functional prediction (Tax4Fun) indicated that Fe exposure enhanced xenobiotic biodegradation, immune diseases, and cell-death–related pathways, while functions associated with energy, amino-acid and carbohydrate metabolism, and nervous system were comparatively downregulated. Collectively, FeSO₄ exposure impaired antioxidant defences, triggered apoptosis, and induced intestinal dysbiosis, with implications for aquaculture health management and environmental risk assessment.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"302 ","pages":"Article 110450"},"PeriodicalIF":4.3,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917009","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}
Florfenicol, a widely used veterinary antibiotic, is increasingly being detected in aquatic environments; however, its potential effects on thyroid hormone (TH) homeostasis remain unclear. This study integrated in vivo zebrafish assays with in silico molecular simulations to investigate the thyroid-disrupting effects of florfenicol and its underlying mechanisms. Exposure to environmentally relevant concentrations of florfenicol significantly reduced plasma T4 and T3 levels in zebrafish. This reduction was linked to dysregulated expression of the hypothalamus-pituitary-thyroid (HPT) axis genes, particularly transthyretin (TTR), deiodinase 2, and deiodinase 3. Additionally, molecular docking and dynamics simulations confirmed that florfenicol can stably bind to TTR and thyroid receptors α and β, with an affinity comparable to or higher than that of natural THs. Overall, these results demonstrate that florfenicol disrupts TH homeostasis by interfering with the HPT axis and directly affecting TH transport and receptor binding. Our study highlights the potential ecological risks of florfenicol to the thyroid endocrine system in aquatic wildlife.
{"title":"Assessment of thyroid endocrine disruption induced by florfenicol: Integrating in vivo zebrafish experiments and in silico molecular docking and dynamics simulations","authors":"Zhongjun Ma , Bingkun Duan , Ying Shen, Huiqing Tian, Fei Zhao, Changqing Liu, Penghao Wei","doi":"10.1016/j.cbpc.2025.110440","DOIUrl":"10.1016/j.cbpc.2025.110440","url":null,"abstract":"<div><div>Florfenicol, a widely used veterinary antibiotic, is increasingly being detected in aquatic environments; however, its potential effects on thyroid hormone (TH) homeostasis remain unclear. This study integrated <em>in vivo</em> zebrafish assays with <em>in silico</em> molecular simulations to investigate the thyroid-disrupting effects of florfenicol and its underlying mechanisms. Exposure to environmentally relevant concentrations of florfenicol significantly reduced plasma T4 and T3 levels in zebrafish. This reduction was linked to dysregulated expression of the hypothalamus-pituitary-thyroid (HPT) axis genes, particularly <em>transthyretin</em> (TTR), <em>deiodinase 2</em>, and <em>deiodinase 3</em>. Additionally, molecular docking and dynamics simulations confirmed that florfenicol can stably bind to TTR and thyroid receptors α and β, with an affinity comparable to or higher than that of natural THs. Overall, these results demonstrate that florfenicol disrupts TH homeostasis by interfering with the HPT axis and directly affecting TH transport and receptor binding. Our study highlights the potential ecological risks of florfenicol to the thyroid endocrine system in aquatic wildlife.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"301 ","pages":"Article 110440"},"PeriodicalIF":4.3,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849105","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 : 2025-12-26DOI: 10.1016/j.cbpc.2025.110441
Da-Hyun Jeong , Rajesh Kumar Pathak , Taeeun Kim , Jun-Mo Kim , Hee-Seok Lee
The veterinary progestin altrenogest is widely used, yet its potential as an endocrine disruptor impacting metabolic health is poorly understood. This study provides the first evidence that altrenogest promotes adipogenesis (lipid accumulation) in vitro by activating estrogen receptor alpha (ERα). We combined computational modeling, which predicted altrenogest binds to ERα, with a validated ERα transcriptional activation assay (hERα-HeLa-9903), which confirmed altrenogest is an ERα agonist. In 3 T3-L1 adipocytes, altrenogest exposure significantly increased lipid accumulation and upregulated key adipogenic and lipogenic transcription factors, such as Pparg and Srebf1. Specifically, altrenogest treatment significantly increased lipid accumulation by approximately 198 % at the highest effective concentration (log M = −5). This adipogenic effect was demonstrated to be ERα-dependent, as co-treatment with the selective ERα antagonist methylpiperidino pyrazole (MPP) significantly attenuated these effects.
These findings present a robust mechanistic link between altrenogest, ERα activation, and pro-adipogenic signaling. This study emphasizes the necessity for stricter regulatory oversight of environmental residues from veterinary progestins, as they may contribute to metabolic disorders such as obesity.
兽药黄体酮阿列诺糖被广泛使用，但其作为内分泌干扰物影响代谢健康的潜力尚不清楚。本研究首次证明阿替诺酯通过激活雌激素受体α (ERα)促进体外脂肪形成（脂质积累）。我们将预测altrenogest与ERα结合的计算模型与经过验证的ERα转录激活试验（hERα-HeLa-9903）相结合，证实altrenogest是ERα激动剂。在3 T3-L1脂肪细胞中，alt - noret暴露显著增加脂质积累，上调关键的成脂和成脂转录因子，如Pparg和Srebf1。具体来说，在最高有效浓度下，阿替诺酯治疗显著增加了约198 %的脂质积累（log M = -5）。这种成脂作用被证明是ERα依赖的，因为与选择性ERα拮抗剂甲基哌啶醇吡唑（MPP）共同治疗可显著减弱这些作用。这些发现显示了altrenogest， ERα激活和促脂肪信号之间的强大机制联系。这项研究强调了对兽医黄体酮环境残留物进行更严格监管的必要性，因为它们可能导致代谢紊乱，如肥胖。
{"title":"Elucidating altrenogest-induced lipid accumulation via estrogen receptor alpha modulation: Insights from computational and cell-based approaches","authors":"Da-Hyun Jeong , Rajesh Kumar Pathak , Taeeun Kim , Jun-Mo Kim , Hee-Seok Lee","doi":"10.1016/j.cbpc.2025.110441","DOIUrl":"10.1016/j.cbpc.2025.110441","url":null,"abstract":"<div><div>The veterinary progestin altrenogest is widely used, yet its potential as an endocrine disruptor impacting metabolic health is poorly understood. This study provides the first evidence that altrenogest promotes adipogenesis (lipid accumulation) in vitro by activating estrogen receptor alpha (ERα). We combined computational modeling, which predicted altrenogest binds to ERα, with a validated ERα transcriptional activation assay (hERα-HeLa-9903), which confirmed altrenogest is an ERα agonist. In 3 T3-L1 adipocytes, altrenogest exposure significantly increased lipid accumulation and upregulated key adipogenic and lipogenic transcription factors, such as <em>Pparg</em> and <em>Srebf1</em>. Specifically, altrenogest treatment significantly increased lipid accumulation by approximately 198 % at the highest effective concentration (log M = −5). This adipogenic effect was demonstrated to be ERα-dependent, as co-treatment with the selective ERα antagonist methylpiperidino pyrazole (MPP) significantly attenuated these effects.</div><div>These findings present a robust mechanistic link between altrenogest, ERα activation, and pro-adipogenic signaling. This study emphasizes the necessity for stricter regulatory oversight of environmental residues from veterinary progestins, as they may contribute to metabolic disorders such as obesity.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"302 ","pages":"Article 110441"},"PeriodicalIF":4.3,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849114","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}
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 (Cmax) 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.
{"title":"Probiotic Enterococcus faecium NCIMB 10415 modulates florfenicol pharmacokinetics, withdrawal time, and hepatic CYP3A activity, potentially lowering antibiotic efficacy in Nile tilapia (Oreochromis niloticus)","authors":"Chi-Ming Wu , Yi-Ping Lu , Tirawat Rairat , Yu-Nan Tsai , Channarong Rodkhum , Prapansak Srisapoome , Chi-Chung Chou","doi":"10.1016/j.cbpc.2025.110438","DOIUrl":"10.1016/j.cbpc.2025.110438","url":null,"abstract":"<div><div>Few studies have examined how probiotics affect drug efficacy in aquaculture. This study investigated impacts of <em>Enterococcus faecium</em> on the pharmacokinetics (PK), tissue residues, and withdrawal time (WDT) of florfenicol (FF) in Nile tilapia. Fish were orally administered <em>E. faecium</em> 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, <em>E. faecium</em>-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<sub>max</sub>) 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. <em>E. faecium</em>-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, <em>E. faecium</em> pretreatment upregulated <em>Cyp3A40</em> in the intestine and liver but did not affect <em>Cyp1A</em> gene, thereby maintaining CYP3A enzyme activities that would otherwise be suppressed by FF. Collectively, these results indicate that <em>E. faecium</em> 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.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"301 ","pages":"Article 110438"},"PeriodicalIF":4.3,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849110","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}
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。
{"title":"Parental exposure to phenanthrene induces thyroid disruption in zebrafish offspring","authors":"Liqiao Zhong , Fengyue Zhu , Luyin Wu , Baoshan Ma , Huijun Ru , Xinbin Duan","doi":"10.1016/j.cbpc.2025.110439","DOIUrl":"10.1016/j.cbpc.2025.110439","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"301 ","pages":"Article 110439"},"PeriodicalIF":4.3,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827114","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 : 2025-12-22DOI: 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.
{"title":"Acute heat stress reprograms the circadian–inflammatory–metabolic axis in Lasiopodomys brandtii","authors":"Xi-Zhi Wang , Ying Li , Chen-Zhu Wang , Zhen-Shan Wang , Xue-Ying Zhang","doi":"10.1016/j.cbpc.2025.110435","DOIUrl":"10.1016/j.cbpc.2025.110435","url":null,"abstract":"<div><div>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 (<em>Lasiopodomys brandtii</em>), 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 (<em>Per2</em> and <em>Cry1</em>) and pro-inflammatory genes (<em>Nfκb or Il1α</em>) in the hypothalamus, liver and brown adipose tissue (BAT), and tissue-specific alterations in thermogenic regulators (<em>Pgc1α</em>). 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 <em>Per2</em> and <em>Cry1</em> 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 <em>Nfκb</em> and <em>Il1α</em>. Network modeling further identified <em>Per2</em> and <em>Bmal1</em> 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.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"301 ","pages":"Article 110435"},"PeriodicalIF":4.3,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827134","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 : 2025-12-20DOI: 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.
{"title":"Intergenerational effects of parental dimefluthrin and microcystins co-exposure on zebrafish: Impaired embryonic and larval development","authors":"Yinhui Xu , Bo Gao , Rongkai Bao , Yafang Shi , Wenhua Li , Peng Xiao","doi":"10.1016/j.cbpc.2025.110437","DOIUrl":"10.1016/j.cbpc.2025.110437","url":null,"abstract":"<div><div>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 <em>anxa5b</em> and <em>hprt1l</em>, 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.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"301 ","pages":"Article 110437"},"PeriodicalIF":4.3,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809630","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 : 2025-12-16DOI: 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.
{"title":"Synergistic effects of high temperature and hypoxia on energy metabolism and physiological homeostasis in the Chinese mitten crab (Eriocheir sinensis)","authors":"Cong Zhang , Dunqian Deng , Huixia Feng , Su Jiang , Zihao Song , Kai Zhang , Longlong Fu , Shaowu Yin","doi":"10.1016/j.cbpc.2025.110436","DOIUrl":"10.1016/j.cbpc.2025.110436","url":null,"abstract":"<div><div>High temperature and hypoxia are critical environmental stressors affecting the intensive aquaculture of the Chinese mitten crab (<em>Eriocheir sinensis</em>). 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 <em>c</em> oxidase and cytochrome <em>c</em>, 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.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"301 ","pages":"Article 110436"},"PeriodicalIF":4.3,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780514","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 : 2025-12-10DOI: 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.
{"title":"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","authors":"Huimin Li , Ziang Wang , Suwei He , Minghui Zhong , Xichen Wang , Weitao Hu , Jingrong Tang , Zhonghao Xiao , Xiaowen Shi , Zigang Cao","doi":"10.1016/j.cbpc.2025.110432","DOIUrl":"10.1016/j.cbpc.2025.110432","url":null,"abstract":"<div><div>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 (<em>il1β</em>, <em>tnf-α</em>, <em>nf-κb</em>, <em>il6</em>) and inhibiting the Wnt/β-catenin signaling pathway (<em>lef1</em>, <em>β-catenin</em>, <em>dkk1</em>, <em>wif1</em>). 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.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"301 ","pages":"Article 110432"},"PeriodicalIF":4.3,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741194","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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