Pub Date : 2026-04-01Epub 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":"2026-04-01","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}
Pub Date : 2026-04-01Epub Date: 2026-01-13DOI: 10.1016/j.cbpc.2026.110453
Md Helal Uddin , Jinnath Rehana Ritu , Som Niyogi , Douglas P. Chivers
The pervasive presence of environmental contaminants in aquatic ecosystems has raised significant concerns regarding their long-term impacts on aquatic organisms, particularly fishes. While ecotoxicological studies have traditionally focused on single-generation or single-life-stage exposures, such approaches may underestimate or overestimate population-level consequences. This review critically evaluates the current state of knowledge on the multigenerational effects of both traditional and emerging contaminants in fishes. The study includes five major contaminant groups: pesticides, pharmaceuticals and personal care products (PPCPs), metals and metalloids, microplastics and plasticizers, and per- and polyfluoroalkyl substances (PFASs). Most multigenerational studies have been conducted on freshwater species, including Danio rerio, Oryzias latipes, Oryzias melastigma, Oncorhynchus mykiss, Menidia beryllina, Nothobranchius furzeri, Pimephales promelas, and Paramisgurnus dabryanus, highlighting a substantial research gap in marine fish species. Findings consistently reveal that multigenerational exposure to these contaminants can lead to developmental, behavioural, reproductive, and neurodevelopmental impairments, which may reduce reproductive success, population growth, and overall fitness. Moreover, emerging evidence points to epigenetic modifications, such as DNA methylation and histone alterations, as potential mechanisms underlying these multigenerational effects. Notably, our review identifies considerable variability across studies, with some contaminants exhibiting pronounced multigenerational toxicity, while others show limited or inconsistent outcomes. Given the increasing global concern over aquatic pollution and its far-reaching effects on biodiversity, food security, and public health, this review underscores the urgent need to integrate multigenerational endpoints into ecological risk assessments.
{"title":"Multigenerational effects of selected environmental contaminants in fishes: A comprehensive review","authors":"Md Helal Uddin , Jinnath Rehana Ritu , Som Niyogi , Douglas P. Chivers","doi":"10.1016/j.cbpc.2026.110453","DOIUrl":"10.1016/j.cbpc.2026.110453","url":null,"abstract":"<div><div>The pervasive presence of environmental contaminants in aquatic ecosystems has raised significant concerns regarding their long-term impacts on aquatic organisms, particularly fishes. While ecotoxicological studies have traditionally focused on single-generation or single-life-stage exposures, such approaches may underestimate or overestimate population-level consequences. This review critically evaluates the current state of knowledge on the multigenerational effects of both traditional and emerging contaminants in fishes. The study includes five major contaminant groups: pesticides, pharmaceuticals and personal care products (PPCPs), metals and metalloids, microplastics and plasticizers, and <em>per</em>- and polyfluoroalkyl substances (PFASs). Most multigenerational studies have been conducted on freshwater species, including <em>Danio rerio</em>, <em>Oryzias latipes</em>, <em>Oryzias melastigma</em>, <em>Oncorhynchus mykiss</em>, <em>Menidia beryllina</em>, <em>Nothobranchius furzeri</em>, <em>Pimephales promelas</em>, and <em>Paramisgurnus dabryanus</em>, highlighting a substantial research gap in marine fish species. Findings consistently reveal that multigenerational exposure to these contaminants can lead to developmental, behavioural, reproductive, and neurodevelopmental impairments, which may reduce reproductive success, population growth, and overall fitness. Moreover, emerging evidence points to epigenetic modifications, such as DNA methylation and histone alterations, as potential mechanisms underlying these multigenerational effects. Notably, our review identifies considerable variability across studies, with some contaminants exhibiting pronounced multigenerational toxicity, while others show limited or inconsistent outcomes. Given the increasing global concern over aquatic pollution and its far-reaching effects on biodiversity, food security, and public health, this review underscores the urgent need to integrate multigenerational endpoints into ecological risk assessments.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"302 ","pages":"Article 110453"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988564","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 : 2026-04-01Epub Date: 2026-01-14DOI: 10.1016/j.cbpc.2026.110451
Domenico Nuzzo , Valerio Zupo , Roberta Esposito , Emanuele Somma , Crescenzo Savarese , Simona Carfagna , Giovanna Salbitani , Simona Panunzi , Marcello Pompa , Andrea De Gaetano , Antonella Girgenti , Laura Palumbo , Pasquale Picone , Maria Costantini
Diatoms are microalgae showing a remarkable functional diversity, but their chemical composition is strongly influenced by environmental factors. Knowledge of benthic diatom physiology remains limited compared to planktonic taxa. Light and temperature are key environmental cues affecting biochemical pathways, suggesting that bioactive compound production may vary under different conditions. This study investigated the influence of four light spectra on the growth and secondary metabolite production of the benthic diatom Cocconeis scutellum var. parva. Led lamps demonstrated to be quite efficient in terms of biomass productivity, promoting a significantly higher biomass production with lower energy consumption. Extracts from cultures were characterized and evaluated for cytotoxicity on human cell lines, antioxidant activity, and radical scavenging capacity. Our results revealed marked differences in bioactivity depending on the light spectrum, with neon lamps and one LED system, rich in red light, promoting the highest biological activity. These findings demonstrate that optimizing light conditions is crucial for enhancing the quality of diatom-derived bioactive compounds. Spectral modulation under constant irradiance specifically altered antioxidant and anti-proliferative activities, highlighting the biotechnological potential of C. scutellum var. parva for medical, pharmaceutical, nutraceutical, cosmeceutical, and aquaculture applications.
硅藻是一种功能多样性显著的微藻，但其化学成分受环境因素的影响较大。与浮游生物分类群相比，底栖硅藻生理学的知识仍然有限。光和温度是影响生物化学途径的关键环境因素，这表明生物活性化合物的产生可能在不同的条件下有所不同。研究了四种光谱对底栖硅藻（Cocconeis scutellum var. parva）生长和次生代谢产物产生的影响。Led灯在生物质生产力方面被证明是相当有效的，以更低的能耗促进了显著更高的生物质生产。对培养物的提取物进行了表征，并对其对人类细胞系的细胞毒性、抗氧化活性和自由基清除能力进行了评估。我们的研究结果显示，不同光谱下的生物活性有显著差异，在霓虹灯和一个LED系统中，富含红光，促进了最高的生物活性。这些发现表明，优化光照条件对于提高硅藻衍生生物活性化合物的质量至关重要。恒定辐照下的光谱调制特别改变了黄颡鱼的抗氧化和抗增殖活性，突出了黄颡鱼在医疗、制药、营养、药妆和水产养殖方面的生物技术潜力。
{"title":"Effects of lighting technologies on the physiology of a marine diatom, Cocconeis scutellum var. parva (Bacillariophyceae): 2. production of antioxidants and other bioactive compounds","authors":"Domenico Nuzzo , Valerio Zupo , Roberta Esposito , Emanuele Somma , Crescenzo Savarese , Simona Carfagna , Giovanna Salbitani , Simona Panunzi , Marcello Pompa , Andrea De Gaetano , Antonella Girgenti , Laura Palumbo , Pasquale Picone , Maria Costantini","doi":"10.1016/j.cbpc.2026.110451","DOIUrl":"10.1016/j.cbpc.2026.110451","url":null,"abstract":"<div><div>Diatoms are microalgae showing a remarkable functional diversity, but their chemical composition is strongly influenced by environmental factors. Knowledge of benthic diatom physiology remains limited compared to planktonic taxa. Light and temperature are key environmental cues affecting biochemical pathways, suggesting that bioactive compound production may vary under different conditions. This study investigated the influence of four light spectra on the growth and secondary metabolite production of the benthic diatom <em>Cocconeis scutellum</em> var. <em>parva</em>. Led lamps demonstrated to be quite efficient in terms of biomass productivity, promoting a significantly higher biomass production with lower energy consumption. Extracts from cultures were characterized and evaluated for cytotoxicity on human cell lines, antioxidant activity, and radical scavenging capacity. Our results revealed marked differences in bioactivity depending on the light spectrum, with neon lamps and one LED system, rich in red light, promoting the highest biological activity. These findings demonstrate that optimizing light conditions is crucial for enhancing the quality of diatom-derived bioactive compounds. Spectral modulation under constant irradiance specifically altered antioxidant and anti-proliferative activities, highlighting the biotechnological potential of <em>C. scutellum</em> var. <em>parva</em> for medical, pharmaceutical, nutraceutical, cosmeceutical, and aquaculture applications.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"302 ","pages":"Article 110451"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974219","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 : 2026-04-01Epub 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":"2026-04-01","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 : 2026-04-01Epub Date: 2026-01-26DOI: 10.1016/j.cbpc.2026.110463
Chang-Hong Cheng , Hai-Peng Qin , Si-Gang Fan , Hong-Ling Ma , Guang-Xin Liu , Dong-Lin Yao , Wen-Fan Luo , Xian-Feng Yang , Zhi-Xun Guo
Rab GTPases are pivotal regulators of organelle trafficking and host immune responses, which are critical for bacterial defense. However, little is known of the function of Rab in crustacean responses to bacterial infection. In this study, a Rab10 gene (Sp-Rab10) was identified from the mud crab Scylla paramamosain. The full open reading frame of consisted of 612 bp, encoding a 203-amino acid polypeptide that shared 98% sequence identity with Portunus trituberculatus Rab10. Quantitative real-time PCR (qRT-PCR) analysis showed that Sp-Rab10 exhibited broad tissue distribution, with the highest expression detected in the hepatopancreas. Notably, Sp-Rab10 expression was markedly up-regulated following V. parahaemolyticus infection, implying its potential involvement in the innate immune response against bacterial challenge. To explore the regulatory mechanism of Sp-Rab10, an RNA interference (RNAi) experiment was conducted. Silencing of Sp-Rab10 resulted in significant down regulation of 3 phagocytosis-related genes (c-type lysozyme, crustin and anti-lipopolysaccharide factor). Additionally, in vivo knockdown of Sp-Rab10 increased bacterial load in the hemolymph and mortality of mud crabs after V. parahaemolyticus infection. Collectively, these findings demonstrated that Sp-Rab10 played a critical role in antimicrobial defense in crustaceans.
{"title":"Rab10 GTPase from the mud crab Scylla paramamosain is involved in the host immune response against V. parahaemolyticus infection","authors":"Chang-Hong Cheng , Hai-Peng Qin , Si-Gang Fan , Hong-Ling Ma , Guang-Xin Liu , Dong-Lin Yao , Wen-Fan Luo , Xian-Feng Yang , Zhi-Xun Guo","doi":"10.1016/j.cbpc.2026.110463","DOIUrl":"10.1016/j.cbpc.2026.110463","url":null,"abstract":"<div><div>Rab GTPases are pivotal regulators of organelle trafficking and host immune responses, which are critical for bacterial defense. However, little is known of the function of Rab in crustacean responses to bacterial infection. In this study, a Rab10 gene (<em>Sp-Rab10</em>) was identified from the mud crab <em>Scylla paramamosain</em>. The full open reading frame of consisted of 612 bp, encoding a 203-amino acid polypeptide that shared 98% sequence identity with <em>Portunus trituberculatus Rab10</em>. Quantitative real-time PCR (qRT-PCR) analysis showed that <em>Sp-Rab10</em> exhibited broad tissue distribution, with the highest expression detected in the hepatopancreas. Notably, <em>Sp-Rab10</em> expression was markedly up-regulated following <em>V. parahaemolyticus</em> infection, implying its potential involvement in the innate immune response against bacterial challenge. To explore the regulatory mechanism of Sp-Rab10, an RNA interference (RNAi) experiment was conducted. Silencing of Sp-Rab10 resulted in significant down regulation of 3 phagocytosis-related genes (<em>c-type lysozyme</em>, <em>crustin</em> and <em>anti-lipopolysaccharide factor</em>). Additionally, in vivo knockdown of <em>Sp-Rab10</em> increased bacterial load in the hemolymph and mortality of mud crabs after <em>V. parahaemolyticus</em> infection. Collectively, these findings demonstrated that <em>Sp-Rab10</em> played a critical role in antimicrobial defense in crustaceans.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"302 ","pages":"Article 110463"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146060591","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 : 2026-04-01Epub Date: 2026-01-10DOI: 10.1016/j.cbpc.2026.110452
Huiling Zheng , Xinyu Huo , Wenwen Zhang , Shuang Lou , Mingyue Li , Chenxi Huang , Kang Yang , Tong Xu , Hongjin Lin
Trimethyltin chloride (TMT) is a highly toxic and environmentally ubiquitous organotin compound. Selenium (Se) mitigates toxin-induced injury by alleviating oxidative stress, whereas mitochondrial DNA (mtDNA) leakage activates pyroptosis and inflammation via the mtDNA–cGAS–STING pathway. Yet, the precise mechanism by which selenium antagonizes TMT-induced renal inflammation in chickens through ROS–mtDNA–cGAS–STING-mediated pyroptosis remains elusive. We generated a chicken TMT model (10 μg kg−1 gavage) ± Se-enriched diet (2 mg kg−1). Primary chicken embryo kidney (CEK) cells were used for in vitro validation. Both in vivo and in vitro data revealed that TMT suppressed antioxidants (CAT, GSH-Px, SOD, T-AOC), raised H2O2/MDA, and provoked excessive ROS. TMT also depolarized mitochondrial membrane potential (ΔΨm), elevated mitochondrial ROS (mtROS), induced mtDNA release, and disturbed mitochondrial dynamics, culminating in severe mitochondrial dysfunction. Cytoplasmic mtDNA activated the cGAS–STING pathway, up-regulating key signaling molecules and increasing pyroptosis markers (Caspase1, NLRP3, GSDMD, IL-18) and pro-inflammatory cytokines (TNF-α, ASC, IL-1β, IL-6). Se supplementation reversed these alterations. Importantly, the Se-mediated protection was abolished by the oxidative stress inducer sanguinarine, the cGAS–STING agonist STING-Agonist 12, or the pyroptosis activator nigericin. Collectively, our results demonstrate that Se alleviates TMT-induced renal pyroptosis and inflammation by reducing ROS, preserving mitochondrial homeostasis, preventing mtDNA leakage, and restraining the cGAS–STING pathway. These findings not only elucidate the molecular basis of TMT nephrotoxicity but also support Na2SeO3 as a candidate therapeutic for TMT-induced kidney injury.
{"title":"Selenium regulates pyroptosis through the ROS-mtDNA-cGAS-STING axis to alleviate trimethyltin chloride-induced inflammation in chicken kidneys","authors":"Huiling Zheng , Xinyu Huo , Wenwen Zhang , Shuang Lou , Mingyue Li , Chenxi Huang , Kang Yang , Tong Xu , Hongjin Lin","doi":"10.1016/j.cbpc.2026.110452","DOIUrl":"10.1016/j.cbpc.2026.110452","url":null,"abstract":"<div><div>Trimethyltin chloride (TMT) is a highly toxic and environmentally ubiquitous organotin compound. Selenium (Se) mitigates toxin-induced injury by alleviating oxidative stress, whereas mitochondrial DNA (mtDNA) leakage activates pyroptosis and inflammation via the mtDNA–cGAS–STING pathway. Yet, the precise mechanism by which selenium antagonizes TMT-induced renal inflammation in chickens through ROS–mtDNA–cGAS–STING-mediated pyroptosis remains elusive. We generated a chicken TMT model (10 μg kg<sup>−1</sup> gavage) ± Se-enriched diet (2 mg kg<sup>−1</sup>). Primary chicken embryo kidney (CEK) cells were used for in vitro validation. Both in vivo and in vitro data revealed that TMT suppressed antioxidants (CAT, GSH-Px, SOD, T-AOC), raised H<sub>2</sub>O<sub>2</sub>/MDA, and provoked excessive ROS. TMT also depolarized mitochondrial membrane potential (ΔΨm), elevated mitochondrial ROS (mtROS), induced mtDNA release, and disturbed mitochondrial dynamics, culminating in severe mitochondrial dysfunction. Cytoplasmic mtDNA activated the cGAS–STING pathway, up-regulating key signaling molecules and increasing pyroptosis markers (Caspase1, NLRP3, GSDMD, IL-18) and pro-inflammatory cytokines (TNF-α, ASC, IL-1β, IL-6). Se supplementation reversed these alterations. Importantly, the Se-mediated protection was abolished by the oxidative stress inducer sanguinarine, the cGAS–STING agonist STING-Agonist 12, or the pyroptosis activator nigericin. Collectively, our results demonstrate that Se alleviates TMT-induced renal pyroptosis and inflammation by reducing ROS, preserving mitochondrial homeostasis, preventing mtDNA leakage, and restraining the cGAS–STING pathway. These findings not only elucidate the molecular basis of TMT nephrotoxicity but also support Na<sub>2</sub>SeO<sub>3</sub> as a candidate therapeutic for TMT-induced kidney injury.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"302 ","pages":"Article 110452"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958684","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 : 2026-04-01Epub Date: 2026-01-12DOI: 10.1016/j.cbpc.2026.110456
Nourhan Elsayed
Chronic arsenic exposure is a major environmental cause of neurotoxicity, linked to oxidative stress and apoptosis. While its toxicity is established, protective strategies are limited. Insulin-like growth factor-1 (IGF-1) is a key neurotrophic factor, but its potential to counteract arsenic-induced neuronal apoptosis and DNA fragmentation remains largely unexplored. The neuroprotective role of IGF-1 against sodium arsenite (NaAsO₂) was investigated in human SH-SY5Y neuroblastoma cells. Differentiated cells were employed to study IGF-1/AKT signaling, while undifferentiated cells were employed for apoptosis assays. Cells were exposed to NaAsO₂ with or without IGF-1 treatment. AKT phosphorylation status at Thr308 and Ser473 was assessed by Western blot. Apoptosis was evaluated via flow cytometric analysis of the sub-G1 population and by immunoblotting for key apoptotic markers, including cleaved caspase-3, cleaved PARP, p53, and Bcl-2. Arsenic exposure significantly suppressed AKT phosphorylation and induced concentration-dependent apoptosis, evidenced by increased p53, cleaved caspase-3, PARP cleavage, and a compensatory increase in Bcl-2. Treatment with IGF-1 significantly attenuated these effects. IGF-1 restored AKT signaling, reduced pro-apoptotic markers (p53, cleaved caspase-3), diminished PARP cleavage, and significantly decreased apoptotic cell death and DNA fragmentation (sub-G1 population). The observed reduction in Bcl-2 following IGF-1 treatment suggests a restoration of apoptotic equilibrium. The findings present novel evidence that IGF-1 confers protection against arsenic-induced neuroapoptosis and DNA fragmentation by reactivating the PI3K/AKT pathway. This reactivation rebalances apoptotic regulators and suppresses p53-mediated apoptosis. The findings highlight IGF-1 signaling as a promising therapeutic target for arsenic-related neuronal damage, warranting further investigation in vivo.
{"title":"IGF-1/AKT signaling attenuates arsenic-induced neuronal apoptosis and DNA fragmentation","authors":"Nourhan Elsayed","doi":"10.1016/j.cbpc.2026.110456","DOIUrl":"10.1016/j.cbpc.2026.110456","url":null,"abstract":"<div><div>Chronic arsenic exposure is a major environmental cause of neurotoxicity, linked to oxidative stress and apoptosis. While its toxicity is established, protective strategies are limited. Insulin-like growth factor-1 (IGF-1) is a key neurotrophic factor, but its potential to counteract arsenic-induced neuronal apoptosis and DNA fragmentation remains largely unexplored. The neuroprotective role of IGF-1 against sodium arsenite (NaAsO₂) was investigated in human SH-SY5Y neuroblastoma cells. Differentiated cells were employed to study IGF-1/AKT signaling, while undifferentiated cells were employed for apoptosis assays. Cells were exposed to NaAsO₂ with or without IGF-1 treatment. AKT phosphorylation status at Thr308 and Ser473 was assessed by Western blot. Apoptosis was evaluated via flow cytometric analysis of the sub-G1 population and by immunoblotting for key apoptotic markers, including cleaved caspase-3, cleaved PARP, p53, and Bcl-2. Arsenic exposure significantly suppressed AKT phosphorylation and induced concentration-dependent apoptosis, evidenced by increased p53, cleaved caspase-3, PARP cleavage, and a compensatory increase in Bcl-2. Treatment with IGF-1 significantly attenuated these effects. IGF-1 restored AKT signaling, reduced pro-apoptotic markers (p53, cleaved caspase-3), diminished PARP cleavage, and significantly decreased apoptotic cell death and DNA fragmentation (sub-G1 population). The observed reduction in Bcl-2 following IGF-1 treatment suggests a restoration of apoptotic equilibrium. The findings present novel evidence that IGF-1 confers protection against arsenic-induced neuroapoptosis and DNA fragmentation by reactivating the PI3K/AKT pathway. This reactivation rebalances apoptotic regulators and suppresses p53-mediated apoptosis. The findings highlight IGF-1 signaling as a promising therapeutic target for arsenic-related neuronal damage, warranting further investigation in vivo.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"302 ","pages":"Article 110456"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974218","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}
Due to the rapid development of the power battery industry, the potential pollution of carbon nanotubes (CNTs) has drawn great attention in recent years. In this study, the toxicity of multi-walled CNTs (MWCNTs) on antioxidant capacity, digestive capacity, and transcriptome in Daphnia magna, which is a model organism of plankton, was conducted. D. magna individuals were exposed to different concentrations (0, 0.53 mg/L, and 5.3 mg/L) of MWCNTs for 48 h. The results showed that 5.3 mg/L MWCNTs induced obvious oxidative stress reflected by significantly increased malondialdehyde content, and significantly decreased activities of superoxide dismutase, catalase, and glutathione. There were marked reductions in digestive enzyme activities, including lipase activity, trypsin activity, and amylase activity, in the 5.3 mg/L-exposed group relative to those in the control group. KEGG function annotation analysis showed that MWCNTs at both concentrations disturbed two pathways, including metabolism of xenobiotics by cytochrome P450 and the fatty acid elongation signaling pathway. However, the protein digestion and absorption pathway was disturbed in the 5.3 mg/L MWCNTs-exposed group but not in the 0.53 mg/L MWCNTs-exposed group. Overall, we deduce that oxidative damage, impairment of detoxification function, and disorders of protein metabolism and lipid metabolism are associated with CNTs toxicity on D. magna.
{"title":"Toxicity and transcriptome sequencing analyses of Daphnia magna under multi-walled carbon nanotubes (MWCNTs) stress","authors":"Jiaqi Shen , Zhenyang Zhang , Xudong Zheng , Pinpin Lv , Yong Huang , Xiaochan Gao","doi":"10.1016/j.cbpc.2026.110460","DOIUrl":"10.1016/j.cbpc.2026.110460","url":null,"abstract":"<div><div>Due to the rapid development of the power battery industry, the potential pollution of carbon nanotubes (CNTs) has drawn great attention in recent years. In this study, the toxicity of multi-walled CNTs (MWCNTs) on antioxidant capacity, digestive capacity, and transcriptome in <em>Daphnia magna</em>, which is a model organism of plankton, was conducted. <em>D. magna</em> individuals were exposed to different concentrations (0, 0.53 mg/L, and 5.3 mg/L) of MWCNTs for 48 h. The results showed that 5.3 mg/L MWCNTs induced obvious oxidative stress reflected by significantly increased malondialdehyde content, and significantly decreased activities of superoxide dismutase, catalase, and glutathione. There were marked reductions in digestive enzyme activities, including lipase activity, trypsin activity, and amylase activity, in the 5.3 mg/L-exposed group relative to those in the control group. KEGG function annotation analysis showed that MWCNTs at both concentrations disturbed two pathways, including metabolism of xenobiotics by cytochrome P450 and the fatty acid elongation signaling pathway. However, the protein digestion and absorption pathway was disturbed in the 5.3 mg/L MWCNTs-exposed group but not in the 0.53 mg/L MWCNTs-exposed group. Overall, we deduce that oxidative damage, impairment of detoxification function, and disorders of protein metabolism and lipid metabolism are associated with CNTs toxicity on <em>D. magna</em>.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"302 ","pages":"Article 110460"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017672","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 : 2026-04-01Epub Date: 2026-01-19DOI: 10.1016/j.cbpc.2026.110457
Zhang Yizhu , Zaynab Mando , Zenab Aldurrah , Roziana Mohamed Hanaphi , Ahmad Syahir Abd Halim Hapiz , Muhammad Ariff Azmi , Adriana Sofia Abdul Latip , Sarah Idris , Azira Muhamad , Fauziahanim Zakaria
Growing evidence indicates that depression is closely associated with disturbances in the gut-brain axis. Although rodent models are currently widely utilised in depression pathophysiology research, the zebrafish (Danio rerio) has become a valuable and promising alternative model species. This study examined changes in neuroendocrine and neurochemical markers associated with behavioural modifications in a zebrafish model of unpredictable chronic stress (UCS). Following a 14-day UCS procedure, the open-field test (OFT), social interaction test (SIT), and light-dark test (LDT) were conducted. Whole-body cortisol and IL-1β levels, along with metabolomics analysis of brain and intestinal tissues, were performed for neuroendocrine and neurochemical assessment. Depression-like behaviours such as increased immobility time (P = 0.0009) and impaired social interaction (P = 0.0306) were observed, alongside elevated levels of cortisol (P < 0.0001) and IL-1β (P = 0.0255). NMR-based metabolomics analysis revealed alterations in valine, alanine, glutamate, and choline in both brain and intestinal tissues in UCS zebrafish, indicating disruption of amino acid metabolism, highlighting the involvement of bidirectional gut-brain axis communication. The glycine, serine, and threonine pathways were most significantly perturbed in UCS zebrafish, suggesting compromised redox homeostasis leads to neuroinflammation in the pathophysiology of depression-related chronic stress related to the gut-brain axis. This study demonstrates that zebrafish is a valuable alternative vertebrate model for exploring the systemic impacts of unpredictable chronic stress (UCS) on the gut-brain axis.
{"title":"Metabolomic insights into gut–brain axis dysregulation under unpredictable chronic stress in zebrafish","authors":"Zhang Yizhu , Zaynab Mando , Zenab Aldurrah , Roziana Mohamed Hanaphi , Ahmad Syahir Abd Halim Hapiz , Muhammad Ariff Azmi , Adriana Sofia Abdul Latip , Sarah Idris , Azira Muhamad , Fauziahanim Zakaria","doi":"10.1016/j.cbpc.2026.110457","DOIUrl":"10.1016/j.cbpc.2026.110457","url":null,"abstract":"<div><div>Growing evidence indicates that depression is closely associated with disturbances in the gut-brain axis. Although rodent models are currently widely utilised in depression pathophysiology research, the zebrafish (<em>Danio rerio</em>) has become a valuable and promising alternative model species. This study examined changes in neuroendocrine and neurochemical markers associated with behavioural modifications in a zebrafish model of unpredictable chronic stress (UCS). Following a 14-day UCS procedure, the open-field test (OFT), social interaction test (SIT), and light-dark test (LDT) were conducted. Whole-body cortisol and IL-1β levels, along with metabolomics analysis of brain and intestinal tissues, were performed for neuroendocrine and neurochemical assessment. Depression-like behaviours such as increased immobility time (<em>P</em> = 0.0009) and impaired social interaction (<em>P</em> = 0.0306) were observed, alongside elevated levels of cortisol (<em>P</em> < 0.0001) and IL-1β (<em>P</em> = 0.0255). NMR-based metabolomics analysis revealed alterations in valine, alanine, glutamate, and choline in both brain and intestinal tissues in UCS zebrafish, indicating disruption of amino acid metabolism, highlighting the involvement of bidirectional gut-brain axis communication. The glycine, serine, and threonine pathways were most significantly perturbed in UCS zebrafish, suggesting compromised redox homeostasis leads to neuroinflammation in the pathophysiology of depression-related chronic stress related to the gut-brain axis. This study demonstrates that zebrafish is a valuable alternative vertebrate model for exploring the systemic impacts of unpredictable chronic stress (UCS) on the gut-brain axis.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"302 ","pages":"Article 110457"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017508","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 : 2026-03-19DOI: 10.1016/j.cbpc.2026.110513
Guang-Zhen Ji, Jing Zhang, Yuan-Fan Zhao, Shu-Guang Zhu, Ren-Yong Jia, Jian-Ping Zeng, Hui-Yan Shen, Jin Zhang
Environmental pollutants with different concentration and toxicity mechanisms often coexist in complex mixed states, threatening the health of environment and human beings. Elucidating the potential toxicity mechanisms is critical for accurate risk assessment of pollutants in the environment. Therefore, toxicity mechanisms of two tetracycline antibiotics, doxycycline hydrochloride (DH) and minocycline (MINO), and two haloacetic acid disinfection byproducts, bromoacetic acid (BAA) and iodoacetic acid (IAA), together with their mixtures to Escherichia coli (E. coli) were investigated in this study. Results indicate mixture ray with the strongest toxicity causes extensive bacterial elongation into rod-like forms, massive leakage of intracellular contents, and the most severe damage. The concentration ratio of IAA in the mixture determines the extent of cell membrane disruption. DH and MINO are known to inhibit bacterial protein synthesis, whereas the two disinfection by-products (DBPs), BAA and IAA, have been reported to induce oxidative stress and protein stress responses in bacteria. In the present study, exposure to these pollutants and their mixtures resulted in significant alterations in cell morphology and membrane-associated characteristics of E. coli, suggesting potential cellular stress responses. Most interestingly, all the individual pollutants and their mixtures can stabilize or alter specific functional groups, and the changes of functional groups and elements in cell membrane closely correlate with pollutants' toxic effects. The regression equation further highlights that the toxicity of chemical contaminants and their mixtures can be effectively evaluated by observing the changing of certain functional group on the cell membrane of test organism.
{"title":"Predictable toxicity of antibiotics and disinfection by-products as well as their mixtures based on the mechanism-oriented analysis.","authors":"Guang-Zhen Ji, Jing Zhang, Yuan-Fan Zhao, Shu-Guang Zhu, Ren-Yong Jia, Jian-Ping Zeng, Hui-Yan Shen, Jin Zhang","doi":"10.1016/j.cbpc.2026.110513","DOIUrl":"10.1016/j.cbpc.2026.110513","url":null,"abstract":"<p><p>Environmental pollutants with different concentration and toxicity mechanisms often coexist in complex mixed states, threatening the health of environment and human beings. Elucidating the potential toxicity mechanisms is critical for accurate risk assessment of pollutants in the environment. Therefore, toxicity mechanisms of two tetracycline antibiotics, doxycycline hydrochloride (DH) and minocycline (MINO), and two haloacetic acid disinfection byproducts, bromoacetic acid (BAA) and iodoacetic acid (IAA), together with their mixtures to Escherichia coli (E. coli) were investigated in this study. Results indicate mixture ray with the strongest toxicity causes extensive bacterial elongation into rod-like forms, massive leakage of intracellular contents, and the most severe damage. The concentration ratio of IAA in the mixture determines the extent of cell membrane disruption. DH and MINO are known to inhibit bacterial protein synthesis, whereas the two disinfection by-products (DBPs), BAA and IAA, have been reported to induce oxidative stress and protein stress responses in bacteria. In the present study, exposure to these pollutants and their mixtures resulted in significant alterations in cell morphology and membrane-associated characteristics of E. coli, suggesting potential cellular stress responses. Most interestingly, all the individual pollutants and their mixtures can stabilize or alter specific functional groups, and the changes of functional groups and elements in cell membrane closely correlate with pollutants' toxic effects. The regression equation further highlights that the toxicity of chemical contaminants and their mixtures can be effectively evaluated by observing the changing of certain functional group on the cell membrane of test organism.</p>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":" ","pages":"110513"},"PeriodicalIF":4.3,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490619","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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