Comparative Biochemistry and Physiology C-toxicology & Pharmacology最新文献_第2页

A conserved gut-brain axis underlies the neurobehavioral toxicity of a high-sugar diet: A mechanistic study in Drosophila 保守的肠脑轴是高糖饮食的神经行为毒性的基础：果蝇的机制研究。

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 : 2026-05-01 Epub Date: 2026-02-02 DOI: 10.1016/j.cbpc.2026.110472

Chenyi Yu , Yingxia Hu , Xinyi Zhou , Qifang Wu , Linya Wu , Haibin Tong , Changcan Jiang

High-sugar diets (HSD) represent a pervasive environmental stressor with significant health risks, yet the comparative toxicology and underlying molecular mechanisms of its impact on the central nervous system remain poorly understood. This study investigated the neurobehavioral toxicity of HSD and elucidated its mechanism of action, utilizing the invertebrate model Drosophila melanogaster to explore conserved physiological responses. Chronic exposure to a 20% HSD induced significant sleep impairment, a key neurobehavioral endpoint, characterized by reduced total sleep time and increased activity duration without affecting core circadian rhythmicity. Mechanistically, we identified a novel, indirect neurotoxic pathway originating in the gut, highlighting a conserved gut-brain axis. HSD exposure acted as a potent disruptor of gut homeostasis, inducing microbiota dysbiosis (notably decreasing Acetobacter aceti abundance) and triggering a robust intestinal inflammatory response, marked by the upregulation of pro-inflammatory cytokines Upd3 and Eiger (homologs of mammalian IL-6 and TNF-α). This peripheral immunotoxicity was causally linked to central neurochemical disruption, leading to significant neurotransmitter imbalances in the brain. Critically, targeting the initial site of toxicity—the gut—by genetically reducing Upd3 or Eiger expression specifically in intestinal epithelial cells was sufficient to rescue both the sleep deficits and the altered neurotransmitter profiles. Furthermore, ameliorating gut dysbiosis via dietary supplementation with A. aceti reversed the intestinal inflammation and normalized sleep behavior. These findings demonstrate that HSD exerts its neurobehavioral toxicity through a conserved gut-brain axis mechanism, where microbiota dysbiosis and intestinal inflammation drive central neurotransmitter dysregulation. This work highlights a critical toxicological pathway for dietary stressors with broad comparative and physiological relevance and identifies the gut inflammatory axis as a potential therapeutic target.

高糖饮食（HSD）是一种普遍存在的环境应激源，具有重大的健康风险，但其对中枢神经系统影响的比较毒理学和潜在的分子机制仍然知之甚少。本研究利用无脊椎动物模型黑腹果蝇，研究HSD的神经行为毒性并阐明其作用机制，探索其保守的生理反应。长期暴露于20%的HSD会导致严重的睡眠障碍，这是一个关键的神经行为终点，其特征是总睡眠时间减少，活动持续时间增加，但不影响核心昼夜节律。在机制上，我们发现了一种新的，间接的神经毒性途径起源于肠道，突出了一个保守的肠-脑轴。HSD暴露是肠道内稳态的有效破坏者，诱导微生物群失调（特别是乙酰杆菌的丰度降低）并引发强烈的肠道炎症反应，其标志是促炎细胞因子Upd3和Eiger（哺乳动物IL-6和TNF-α的同源物）的上调。这种外周免疫毒性与中枢神经化学破坏有因果关系，导致大脑中显著的神经递质失衡。关键的是，通过在肠道上皮细胞中特异性地减少Upd3或Eiger的表达来靶向毒性的初始部位——肠道，足以挽救睡眠不足和改变的神经递质特征。此外，通过膳食补充乙酰A.醋酸乙酯来改善肠道生态失调，可以逆转肠道炎症并使睡眠行为正常化。这些发现表明，HSD通过保守的肠-脑轴机制发挥其神经行为毒性，其中微生物群失调和肠道炎症驱动中枢神经递质失调。这项工作强调了饮食应激源具有广泛的比较和生理相关性的关键毒理学途径，并确定了肠道炎症轴作为潜在的治疗靶点。

{"title":"A conserved gut-brain axis underlies the neurobehavioral toxicity of a high-sugar diet: A mechanistic study in Drosophila","authors":"Chenyi Yu , Yingxia Hu , Xinyi Zhou , Qifang Wu , Linya Wu , Haibin Tong , Changcan Jiang","doi":"10.1016/j.cbpc.2026.110472","DOIUrl":"10.1016/j.cbpc.2026.110472","url":null,"abstract":"<div><div>High-sugar diets (HSD) represent a pervasive environmental stressor with significant health risks, yet the comparative toxicology and underlying molecular mechanisms of its impact on the central nervous system remain poorly understood. This study investigated the neurobehavioral toxicity of HSD and elucidated its mechanism of action, utilizing the invertebrate model <em>Drosophila melanogaster</em> to explore conserved physiological responses. Chronic exposure to a 20% HSD induced significant sleep impairment, a key neurobehavioral endpoint, characterized by reduced total sleep time and increased activity duration without affecting core circadian rhythmicity. Mechanistically, we identified a novel, indirect neurotoxic pathway originating in the gut, highlighting a conserved gut-brain axis. HSD exposure acted as a potent disruptor of gut homeostasis, inducing microbiota dysbiosis (notably decreasing <em>Acetobacter aceti</em> abundance) and triggering a robust intestinal inflammatory response, marked by the upregulation of pro-inflammatory cytokines Upd3 and Eiger (homologs of mammalian IL-6 and TNF-α). This peripheral immunotoxicity was causally linked to central neurochemical disruption, leading to significant neurotransmitter imbalances in the brain. Critically, targeting the initial site of toxicity—the gut—by genetically reducing <em>Upd3</em> or <em>Eiger</em> expression specifically in intestinal epithelial cells was sufficient to rescue both the sleep deficits and the altered neurotransmitter profiles. Furthermore, ameliorating gut dysbiosis via dietary supplementation with <em>A. aceti</em> reversed the intestinal inflammation and normalized sleep behavior. These findings demonstrate that HSD exerts its neurobehavioral toxicity through a conserved gut-brain axis mechanism, where microbiota dysbiosis and intestinal inflammation drive central neurotransmitter dysregulation. This work highlights a critical toxicological pathway for dietary stressors with broad comparative and physiological relevance and identifies the gut inflammatory axis as a potential therapeutic target.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"303 ","pages":"Article 110472"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118215","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}

引用次数: 0

Lupiwighteone exerts anti-aging effects by suppressing NF-κB and activating the MAPKs/Nrf2 signaling pathway lupiwhighteone通过抑制NF-κB和激活MAPKs/Nrf2信号通路发挥抗衰老作用

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 : 2026-05-01 Epub Date: 2026-01-26 DOI: 10.1016/j.cbpc.2026.110458

Kun Hu , Ge Ge , Bingjian Wu , Jia Yang , Jie Ren , Lirong Zhang

Lupiwighteone (Lup), a natural isoflavonoid, phytochemical, exhibits potential anti-inflammatory properties; however, its impacts on inflammation, oxidative stress, and aging processes remain insufficiently characterized. The present study systematically investigated the anti-inflammatory and anti-aging effects of Lup using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and Caenorhabditis elegans (C. elegans), aiming to elucidate its underlying molecular mechanisms and biological significance. The study employed cell culture, animal experiments, and molecular biology techniques, combined with molecular docking, to evaluate Lup's modulatory effects on NF-κB and MAPK signaling cascades and the Nrf2 pathway. Our results indicated that Lup treatment significantly extended lifespan, reduced reactive oxygen species (ROS) levels, and slowed age-related physiological decline in the C. elegans model. Mechanistically, we found that Lup activated the MAPKs/Nrf2 pathway, enhanced antioxidant stress responses, and reduced oxidative damage, thereby delaying the aging process. Additionally, Lup treatment significantly suppressed the production and secretion of key pro-inflammatory mediators, including TNF-α, IL-6, and nitric oxide, while inhibiting NF-κB signaling activation in LPS-stimulated RAW264.7 cells. This inhibition was mediated by impeding IκBα degradation, thereby preventing NF-κB translocation to the nucleus. Collectively, these findings demonstrated that Lup exerts significant anti-aging, anti-inflammatory, and antioxidant activities through the dual regulation of oxidative stress and inflammation. These results not only strengthen the theoretical basis of plant-derived medicines in anti-inflammation and anti-aging but also provide new insights and practical guidance for the future development of natural pharmaceuticals.

lupiwhighteone （Lup）是一种天然的异黄酮类化合物，具有潜在的抗炎特性；然而，其对炎症、氧化应激和衰老过程的影响尚未得到充分的研究。本研究利用脂多糖（LPS）刺激的RAW264.7巨噬细胞和秀丽隐杆线虫（C. elegans），系统研究了Lup的抗炎和抗衰老作用，旨在阐明其潜在的分子机制和生物学意义。本研究采用细胞培养、动物实验和分子生物学技术，结合分子对接，评估Lup对NF-κB和MAPK信号级联以及Nrf2通路的调节作用。我们的研究结果表明，Lup治疗显著延长了秀丽隐杆线虫模型的寿命，降低了活性氧（ROS）水平，减缓了与年龄相关的生理衰退。在机制上，我们发现Lup激活了MAPKs/Nrf2通路，增强了抗氧化应激反应，减少了氧化损伤，从而延缓了衰老过程。此外，Lup处理显著抑制关键促炎介质的产生和分泌，包括TNF-α、IL-6和一氧化氮，同时抑制lps刺激的RAW264.7细胞中NF-κB信号的激活。这种抑制是通过阻碍i -κB α降解介导的，从而阻止NF-κB易位到细胞核。综上所述，这些发现表明，Lup通过对氧化应激和炎症的双重调节，具有显著的抗衰老、抗炎和抗氧化活性。这些结果不仅强化了植物源性药物抗炎抗衰老的理论基础，也为未来天然药物的开发提供了新的见解和实践指导。

{"title":"Lupiwighteone exerts anti-aging effects by suppressing NF-κB and activating the MAPKs/Nrf2 signaling pathway","authors":"Kun Hu , Ge Ge , Bingjian Wu , Jia Yang , Jie Ren , Lirong Zhang","doi":"10.1016/j.cbpc.2026.110458","DOIUrl":"10.1016/j.cbpc.2026.110458","url":null,"abstract":"<div><div>Lupiwighteone (Lup), a natural isoflavonoid, phytochemical, exhibits potential anti-inflammatory properties; however, its impacts on inflammation, oxidative stress, and aging processes remain insufficiently characterized. The present study systematically investigated the anti-inflammatory and anti-aging effects of Lup using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and <em>Caenorhabditis elegans</em> (<em>C. elegans</em>), aiming to elucidate its underlying molecular mechanisms and biological significance. The study employed cell culture, animal experiments, and molecular biology techniques, combined with molecular docking, to evaluate Lup's modulatory effects on NF-κB and MAPK signaling cascades and the Nrf2 pathway. Our results indicated that Lup treatment significantly extended lifespan, reduced reactive oxygen species (ROS) levels, and slowed age-related physiological decline in the <em>C. elegans</em> model. Mechanistically, we found that Lup activated the MAPKs/Nrf2 pathway, enhanced antioxidant stress responses, and reduced oxidative damage, thereby delaying the aging process. Additionally, Lup treatment significantly suppressed the production and secretion of key pro-inflammatory mediators, including TNF-α, IL-6, and nitric oxide, while inhibiting NF-κB signaling activation in LPS-stimulated RAW264.7 cells. This inhibition was mediated by impeding IκBα degradation, thereby preventing NF-κB translocation to the nucleus. Collectively, these findings demonstrated that Lup exerts significant anti-aging, anti-inflammatory, and antioxidant activities through the dual regulation of oxidative stress and inflammation. These results not only strengthen the theoretical basis of plant-derived medicines in anti-inflammation and anti-aging but also provide new insights and practical guidance for the future development of natural pharmaceuticals.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"303 ","pages":"Article 110458"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077064","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}

引用次数: 0

The silent saboteurs: How ultraviolet (UV)-aged polystyrene nanoplastics disrupt the regenerative capacity of goldfish (Carassius auratus) caudal fins 沉默的破坏者：紫外线（UV）老化的聚苯乙烯纳米塑料如何破坏金鱼（Carassius auratus）尾鳍的再生能力。

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 : 2026-05-01 Epub Date: 2026-01-23 DOI: 10.1016/j.cbpc.2026.110462

Deshan Chen , Tian Wang , Lei Han , Hongwei Wang , Mohammad Mehdi Ommati , Ping Sun

Nanoplastics (NPs) are emerging as significant environmental hazards, especially in aquatic ecosystems, where they predominantly exist in aged forms due to weathering processes. Fish, known for their remarkable ability to regenerate injured caudal fins through intricate biological mechanisms, serve as an ideal model for studying sublethal effects of environmental pollutants. This study investigates the toxic impacts of aged polystyrene nanoplastics (PS-NPs) on caudal fin regeneration in goldfish, focusing on molecular, cellular, and physiological responses. Goldfish were exposed to UV-aged PS-NPs (50 nm) at concentrations of 0, 10, 100, and 1000 μg/L, and regeneration was monitored at 7-, 14-, and 35 days post-amputation (dpa). Results demonstrated that caudal fin regeneration was significantly impaired in a concentration- and time-dependent manner. Under exposure to a low concentration (10 μg/L) of aged PS-NPs, goldfish showed an adaptive antioxidant response. Exposure to medium-high concentrations (100–1000 μg/L) led to abnormal ROS activity, disordered apoptosis, and abnormal transcription of core genes in oxidative stress (gpx, sod), immune-inflammation (mpeg1, il-1β, tnf-α), and regeneration pathways (fgf20a, runx2a). This ultimately led to a significant inhibition of caudal fin regeneration at 35 dpa. This study indicates that UV-aged PS-NPs can inhibit the regeneration of goldfish tail fins by disrupting the coordinated function of the oxidative stress-immune-apoptosis-regeneration pathway. The study highlights the risks posed by aged NPs in aquatic environments, emphasizing their potential to impair critical tissue regeneration processes in fish, with broader implications for ecosystem health and resilience.

纳米塑料（NPs）正在成为严重的环境危害，特别是在水生生态系统中，由于风化过程，它们主要以老化形式存在。鱼类以其通过复杂的生物机制再生受伤尾鳍的非凡能力而闻名，是研究环境污染物亚致死效应的理想模型。本研究探讨了老化聚苯乙烯纳米塑料（PS-NPs）对金鱼尾鳍再生的毒性影响，重点研究了分子、细胞和生理反应。将金鱼暴露于浓度为0、10、100和1000 μg/L的uv老化PS-NPs（50 nm）中，并在截肢后7、14和35 天（dpa）监测再生情况。结果表明，尾鳍再生明显受损，且具有浓度和时间依赖性。在低浓度（10 μg/L）老化PS-NPs下，金鱼表现出适应性抗氧化反应。中高浓度（100-1000 μg/L）暴露导致ROS活性异常，细胞凋亡紊乱，氧化应激（gpx、sod）、免疫炎症（mpeg1、il-1β、tnf-α）和再生途径（fgf20a、runx2a）核心基因转录异常。这最终导致35 dpa时尾鳍再生的显著抑制。本研究表明，uv老化的PS-NPs可以通过破坏氧化应激-免疫-凋亡-再生途径的协调功能来抑制金鱼尾鳍的再生。该研究强调了水生环境中老化NPs带来的风险，强调了它们可能损害鱼类关键组织再生过程，对生态系统健康和恢复力具有更广泛的影响。

{"title":"The silent saboteurs: How ultraviolet (UV)-aged polystyrene nanoplastics disrupt the regenerative capacity of goldfish (Carassius auratus) caudal fins","authors":"Deshan Chen , Tian Wang , Lei Han , Hongwei Wang , Mohammad Mehdi Ommati , Ping Sun","doi":"10.1016/j.cbpc.2026.110462","DOIUrl":"10.1016/j.cbpc.2026.110462","url":null,"abstract":"<div><div>Nanoplastics (NPs) are emerging as significant environmental hazards, especially in aquatic ecosystems, where they predominantly exist in aged forms due to weathering processes. Fish, known for their remarkable ability to regenerate injured caudal fins through intricate biological mechanisms, serve as an ideal model for studying sublethal effects of environmental pollutants. This study investigates the toxic impacts of aged polystyrene nanoplastics (PS-NPs) on caudal fin regeneration in goldfish, focusing on molecular, cellular, and physiological responses. Goldfish were exposed to UV-aged PS-NPs (50 nm) at concentrations of 0, 10, 100, and 1000 μg/L, and regeneration was monitored at 7-, 14-, and 35 days post-amputation (dpa). Results demonstrated that caudal fin regeneration was significantly impaired in a concentration- and time-dependent manner. Under exposure to a low concentration (10 μg/L) of aged PS-NPs, goldfish showed an adaptive antioxidant response. Exposure to medium-high concentrations (100–1000 μg/L) led to abnormal ROS activity, disordered apoptosis, and abnormal transcription of core genes in oxidative stress (<em>gpx</em>, <em>sod</em>), immune-inflammation (<em>mpeg1</em>, <em>il-1β</em>, <em>tnf-α</em>), and regeneration pathways (<em>fgf20a</em>, <em>runx2a</em>). This ultimately led to a significant inhibition of caudal fin regeneration at 35 dpa. This study indicates that UV-aged PS-NPs can inhibit the regeneration of goldfish tail fins by disrupting the coordinated function of the oxidative stress-immune-apoptosis-regeneration pathway. The study highlights the risks posed by aged NPs in aquatic environments, emphasizing their potential to impair critical tissue regeneration processes in fish, with broader implications for ecosystem health and resilience.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"303 ","pages":"Article 110462"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046269","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}

引用次数: 0

Microplastics and bisphenol A co-exposure causes oxidative damage and induces ion regulation disorders in the gills of Portunus trituberculatus 微塑料和双酚A共同暴露会引起三瘤梭子鱼鳃的氧化损伤和离子调节紊乱。

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 : 2026-05-01 Epub Date: 2026-02-02 DOI: 10.1016/j.cbpc.2026.110475

Xiaotian Wang , Zhengjia Wei , Xunjie Huo , Xuerui Ge , Jiayuan Ren , Xiaocong Chen , Tao Zhang

Microplastics have been established as a novel environmental contaminant, while bisphenol A represents a common endocrine-disrupting chemical. However, the combined toxicity of both pollutants on the gills of marine crustaceans remains underexplored. This study investigated the possible risks associated with co-exposure to MPs and BPA on the gills of Portunus trituberculatus. Crabs were exposed to 100 μg/L BPA, 10 mg/L MPs, and a combination of 100 μg/L BPA + 10 mg/L MPs for 21 days. Histological analysis revealed that both MPs and BPA significantly compromised gill architecture. Transcriptomic analysis identified 1766 differentially expressed transcripts under varying exposure conditions, which were implicated in biological processes associated with oxidative stress, ion regulation, and apoptosis. The presence of MPs, BPA, and their co-exposure resulted in a reduction of sodium/potassium-transporting ATPase subunit beta-1 expression levels, ATPase activities, ATP content, and ion concentrations in the gills when compared to the control group. Notably, MPs, BPA and their combined treatment induced ROS and H₂O₂ accumulation, and the upregulation of catalase and superoxide dismutase activities, which could potentially impact cell apoptosis. These results suggest that MPs and BPA may adversely affect oxidative damage, ion content, ion regulatory proteins, ion transport ATPase activity, apoptosis and their related gene expression in the gills of P. trituberculatus. Besides, integrated biomarker response values indicated that co-treatment resulted in greater gill toxicity. This comprehensive understanding highlights the imperative for preemptive measures to mitigate the adverse effects of environmental pollutants on ecological health, while providing valuable insights into the relevant molecular pathways.

微塑料已被确定为一种新的环境污染物，而双酚a则是一种常见的内分泌干扰化学物质。然而，这两种污染物对海洋甲壳类动物鳃的综合毒性仍未得到充分研究。本研究调查了三瘤梭子鱼鳃上MPs和BPA共同暴露的可能风险。螃蟹分别暴露于100 μg/L BPA、10 mg/L MPs和100 μg/L BPA + 10 mg/L MPs的组合中21天。组织学分析显示MPs和BPA都显著损害了鳃结构。转录组学分析确定了1766个不同暴露条件下差异表达的转录物，这些转录物涉及与氧化应激、离子调节和细胞凋亡相关的生物过程。与对照组相比，MPs、BPA的存在和它们的共同暴露导致鳃中钠/钾转运ATP酶亚基β -1表达水平、ATP酶活性、ATP含量和离子浓度的降低。值得注意的是，MPs、BPA及其联合处理可诱导ROS和H2O2积累，并上调过氧化氢酶和超氧化物歧化酶活性，从而可能影响细胞凋亡。这些结果表明，MPs和BPA可能对三瘤鱼鳃的氧化损伤、离子含量、离子调节蛋白、离子转运atp酶活性、细胞凋亡及其相关基因表达产生不利影响。此外，综合生物标志物反应值表明，共同处理导致更大的鳃毒性。这种全面的理解强调了采取先发制人的措施减轻环境污染物对生态健康的不利影响的必要性，同时为相关的分子途径提供了有价值的见解。

{"title":"Microplastics and bisphenol A co-exposure causes oxidative damage and induces ion regulation disorders in the gills of Portunus trituberculatus","authors":"Xiaotian Wang , Zhengjia Wei , Xunjie Huo , Xuerui Ge , Jiayuan Ren , Xiaocong Chen , Tao Zhang","doi":"10.1016/j.cbpc.2026.110475","DOIUrl":"10.1016/j.cbpc.2026.110475","url":null,"abstract":"<div><div>Microplastics have been established as a novel environmental contaminant, while bisphenol A represents a common endocrine-disrupting chemical. However, the combined toxicity of both pollutants on the gills of marine crustaceans remains underexplored. This study investigated the possible risks associated with co-exposure to MPs and BPA on the gills of <em>Portunus trituberculatus</em>. Crabs were exposed to 100 μg/L BPA, 10 mg/L MPs, and a combination of 100 μg/L BPA + 10 mg/L MPs for 21 days. Histological analysis revealed that both MPs and BPA significantly compromised gill architecture. Transcriptomic analysis identified 1766 differentially expressed transcripts under varying exposure conditions, which were implicated in biological processes associated with oxidative stress, ion regulation, and apoptosis. The presence of MPs, BPA, and their co-exposure resulted in a reduction of sodium/potassium-transporting ATPase subunit beta-1 expression levels, ATPase activities, ATP content, and ion concentrations in the gills when compared to the control group. Notably, MPs, BPA and their combined treatment induced ROS and H<sub>2</sub>O<sub>2</sub> accumulation, and the upregulation of catalase and superoxide dismutase activities, which could potentially impact cell apoptosis. These results suggest that MPs and BPA may adversely affect oxidative damage, ion content, ion regulatory proteins, ion transport ATPase activity, apoptosis and their related gene expression in the gills of <em>P. trituberculatus</em>. Besides, integrated biomarker response values indicated that co-treatment resulted in greater gill toxicity. This comprehensive understanding highlights the imperative for preemptive measures to mitigate the adverse effects of environmental pollutants on ecological health, while providing valuable insights into the relevant molecular pathways.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"303 ","pages":"Article 110475"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112370","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}

引用次数: 0

High-concentration polyethylene and polystyrene microplastics co-exposure shorten insect lifespan and impose ecological risk: Multi-omics evidence from Drosophila melanogaster 高浓度聚乙烯和聚苯乙烯微塑料共同暴露缩短昆虫寿命并施加生态风险：来自黑腹果蝇的多组学证据。

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 : 2026-05-01 Epub Date: 2026-02-02 DOI: 10.1016/j.cbpc.2026.110474

Yingyu Liu , Cheng Wang , Caixia Wang , Longhuan Fu , Yunbo Zhang , Zhuo Gao , Zhugen Yang , Fanyu Meng

Microplastics (MPs) are pervasive environmental pollutants, accumulating in ecosystems and posing a long-term exposure risk to both the entire ecosystem and human health. However, the combined impact of such high doses on insect longevity and the consequent ecological consequences remain understudied. Here we used Drosophila melanogaster as a model to quantify lifespan shortening under environmentally realistic and extreme concentrations of Polyethylene (PE) and Polystyrene (PS) co-exposures and to unravel the molecular bases of the observed toxicity. Furthermore, we delved into the underlying mechanism through metabolomics and transcriptomics analysis. Our results demonstrated PE and PS MPs co-exposure with greatly high concentrations significantly reduced the lifespan of Drosophila and influenced age-related phenotypes such as climbing ability, intestinal barrier and hunger resistance. We found that differential metabolites were engaged in various metabolic pathways, including ABC transporters, alanine, aspartate and glutamate metabolism. Differentially expressed genes (DEGs) were closely related to Toll and Imd signaling pathway and Longevity regulating pathway. Gram-level PE and PS co-exposure triggers immune-metabolic crosstalk failure and represents a realistic terrestrial risk factor for insect longevity. Our data highlight the urgent need to include high-dose microplastic mixtures in terrestrial ecotoxicological risk assessments and biodiversity conservation strategies.

Synopsis

Co-exposure to PE and PS MPs with high concentrations induces changes in gene expression and metabolites associated with immune system and energy metabolism in Drosophila, thereby affecting their lifespan.

微塑料是普遍存在的环境污染物，在生态系统中积累，对整个生态系统和人类健康构成长期暴露风险。然而，如此高剂量对昆虫寿命的综合影响以及随之而来的生态后果仍未得到充分研究。本研究以黑腹果蝇（Drosophila melanogaster）为模型，量化了在环境现实和极端浓度的聚乙烯（PE）和聚苯乙烯（PS）共同暴露下的寿命缩短，并揭示了所观察到的毒性的分子基础。此外，我们通过代谢组学和转录组学分析深入研究了潜在的机制。我们的研究结果表明，PE和PS MPs在高浓度下共同暴露会显著降低果蝇的寿命，并影响与年龄相关的表型，如攀爬能力、肠道屏障和饥饿抵抗能力。我们发现差异代谢物参与多种代谢途径，包括ABC转运蛋白、丙氨酸、天冬氨酸和谷氨酸代谢。差异表达基因（DEGs）与Toll和Imd信号通路以及长寿调节通路密切相关。克水平的PE和PS共同暴露引发免疫代谢串扰失效，代表了昆虫寿命的现实陆地风险因素。我们的数据强调迫切需要将高剂量微塑料混合物纳入陆地生态毒理学风险评估和生物多样性保护战略。摘要：共同暴露于高浓度PE和PS MPs可诱导果蝇免疫系统和能量代谢相关的基因表达和代谢物发生变化，从而影响果蝇的寿命。

{"title":"High-concentration polyethylene and polystyrene microplastics co-exposure shorten insect lifespan and impose ecological risk: Multi-omics evidence from Drosophila melanogaster","authors":"Yingyu Liu , Cheng Wang , Caixia Wang , Longhuan Fu , Yunbo Zhang , Zhuo Gao , Zhugen Yang , Fanyu Meng","doi":"10.1016/j.cbpc.2026.110474","DOIUrl":"10.1016/j.cbpc.2026.110474","url":null,"abstract":"<div><div>Microplastics (MPs) are pervasive environmental pollutants, accumulating in ecosystems and posing a long-term exposure risk to both the entire ecosystem and human health. However, the combined impact of such high doses on insect longevity and the consequent ecological consequences remain understudied. Here we used <em>Drosophila melanogaster</em> as a model to quantify lifespan shortening under environmentally realistic and extreme concentrations of Polyethylene (PE) and Polystyrene (PS) co-exposures and to unravel the molecular bases of the observed toxicity. Furthermore, we delved into the underlying mechanism through metabolomics and transcriptomics analysis. Our results demonstrated PE and PS MPs co-exposure with greatly high concentrations significantly reduced the lifespan of <em>Drosophila</em> and influenced age-related phenotypes such as climbing ability, intestinal barrier and hunger resistance. We found that differential metabolites were engaged in various metabolic pathways, including ABC transporters, alanine, aspartate and glutamate metabolism. Differentially expressed genes (DEGs) were closely related to Toll and Imd signaling pathway and Longevity regulating pathway. Gram-level PE and PS co-exposure triggers immune-metabolic crosstalk failure and represents a realistic terrestrial risk factor for insect longevity. Our data highlight the urgent need to include high-dose microplastic mixtures in terrestrial ecotoxicological risk assessments and biodiversity conservation strategies.</div></div><div><h3>Synopsis</h3><div>Co-exposure to PE and PS MPs with high concentrations induces changes in gene expression and metabolites associated with immune system and energy metabolism in <em>Drosophila</em>, thereby affecting their lifespan.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"303 ","pages":"Article 110474"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118227","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}

引用次数: 0

Rare earth element erbium induces hepatotoxicity in zebrafish 稀土元素铒诱导斑马鱼肝毒性。

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 : 2026-05-01 Epub Date: 2026-02-02 DOI: 10.1016/j.cbpc.2026.110476

Xinhao Ye , Mijia Li , Hao Wang , Shuhui Liu , Shimei Xiao , Wei Yuan , Yan Zhao , Keyuan Zhong

Rare earth elements (REEs) are collectively referred to as scandium, yttrium and 15 lanthanide metals in the periodic table. Due to their unique photoelectric and magnetic properties, they are widely used in permanent magnets, new energy and cutting-edge defense technologies. However, large-scale mining and utilization of REEs have led to a significant increase in their concentration in the environment. In the environment, these REEs are regarded as emerging contaminants (ECs). Erbium (Er), a rare earth element of the lanthanide series, is widely used in ceramics, optical fibers, and the nuclear industry. Currently, research on the ecotoxicity of erbium is limited, and its target organs of action remain unclear. In this study, zebrafish were used as experimental animals, and acute exposure experiments were conducted by exposing 72 hpf zebrafish larvae to different concentrations of erbium chloride solution to explore the ecotoxicity of erbium. The main research results are as follows: (1) Exposure to erbium causes abnormal liver development in zebrafish larvae and the liver area of the erbium-exposed group was smaller than that of the control group. (2) Erbium affects liver lipid metabolism, leading to lipid accumulation in the liver of zebrafish larvae, and increasing the contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC) and triglycerides (TG). (3) Exposure to erbium leads to an increase in ROS levels in the liver, and the upregulated expression of the sod1 and sod2 genes. (4) The Keap1/Nrf2 pathway inhibitor resveratrol can effectively alleviate liver lipid accumulation, reduce oxidative stress in the liver and alleviate the liver damage induced by erbium. This study discovered that erbium causes abnormal liver function in zebrafish larvae, suggesting that it might cause liver damage in zebrafish through the ROS-mediated Keap1/Nrf2 pathway. These findings contribute to a more comprehensive understanding of the impact of rare earth elements on the ecosystem and provide a scientific basis for related environmental protection policies.

稀土元素（ree）在元素周期表中统称为钪、钇和15种镧系金属。由于其独特的光电和磁性能，被广泛应用于永磁体、新能源和尖端国防技术中。然而，稀土的大规模开采和利用导致其在环境中的浓度显著增加。在环境中，这些稀土元素被视为新兴污染物（ECs）。铒（Er）是镧系元素中的稀土元素，广泛用于陶瓷、光纤和核工业。目前，对铒的生态毒性研究有限，其作用的靶器官也不清楚。本研究以斑马鱼为实验动物，将72只受精后 h的斑马鱼幼体暴露于不同浓度的氯化铒溶液中，进行急性暴露实验，探讨铒的生态毒性。主要研究结果如下：(1)接触铒引起斑马鱼幼鱼肝脏发育异常，接触铒组肝脏面积小于对照组。(2)铒影响肝脏脂质代谢，导致斑马鱼幼鱼肝脏脂质积累，增加了斑马鱼幼鱼肝脏中丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、总胆固醇（TC）和甘油三酯（TG）的含量。(3)暴露于铒可导致肝脏ROS水平升高，sod1和sod2基因表达上调。(4) Keap1/Nrf2通路抑制剂白藜芦醇能有效缓解肝脏脂质积累，降低肝脏氧化应激，减轻铒对肝脏的损害。本研究发现，铒可引起斑马鱼幼体肝功能异常，提示其可能通过ros介导的Keap1/Nrf2通路引起斑马鱼肝脏损伤。这些发现有助于更全面地认识稀土元素对生态系统的影响，并为相关的环境保护政策提供科学依据。

{"title":"Rare earth element erbium induces hepatotoxicity in zebrafish","authors":"Xinhao Ye , Mijia Li , Hao Wang , Shuhui Liu , Shimei Xiao , Wei Yuan , Yan Zhao , Keyuan Zhong","doi":"10.1016/j.cbpc.2026.110476","DOIUrl":"10.1016/j.cbpc.2026.110476","url":null,"abstract":"<div><div>Rare earth elements (REEs) are collectively referred to as scandium, yttrium and 15 lanthanide metals in the periodic table. Due to their unique photoelectric and magnetic properties, they are widely used in permanent magnets, new energy and cutting-edge defense technologies. However, large-scale mining and utilization of REEs have led to a significant increase in their concentration in the environment. In the environment, these REEs are regarded as emerging contaminants (ECs). Erbium (Er), a rare earth element of the lanthanide series, is widely used in ceramics, optical fibers, and the nuclear industry. Currently, research on the ecotoxicity of erbium is limited, and its target organs of action remain unclear. In this study, zebrafish were used as experimental animals, and acute exposure experiments were conducted by exposing 72 hpf zebrafish larvae to different concentrations of erbium chloride solution to explore the ecotoxicity of erbium. The main research results are as follows: (1) Exposure to erbium causes abnormal liver development in zebrafish larvae and the liver area of the erbium-exposed group was smaller than that of the control group. (2) Erbium affects liver lipid metabolism, leading to lipid accumulation in the liver of zebrafish larvae, and increasing the contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC) and triglycerides (TG). (3) Exposure to erbium leads to an increase in ROS levels in the liver, and the upregulated expression of the <em>sod1</em> and <em>sod2</em> genes. (4) The Keap1/Nrf2 pathway inhibitor resveratrol can effectively alleviate liver lipid accumulation, reduce oxidative stress in the liver and alleviate the liver damage induced by erbium. This study discovered that erbium causes abnormal liver function in zebrafish larvae, suggesting that it might cause liver damage in zebrafish through the ROS-mediated Keap1/Nrf2 pathway. These findings contribute to a more comprehensive understanding of the impact of rare earth elements on the ecosystem and provide a scientific basis for related environmental protection policies.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"303 ","pages":"Article 110476"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118217","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}

引用次数: 0

Beyond molting disruption: Tebufenozide modifies gut immunity and antiviral responses in Helicoverpa armigera (Noctuidae) 除蜕皮破坏外：虫酰肼改变棉铃虫（夜蛾科）的肠道免疫和抗病毒反应。

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 : 2026-05-01 Epub Date: 2026-01-12 DOI: 10.1016/j.cbpc.2026.110455

Marzieh Attarianfar , Azam Mikani , Mohammad Mehrabadi

The insect growth regulator tebufenozide, an ecdysone agonist, is widely used to control Helicoverpa armigera through disrupting molting and development. However, its other effects on the insect physiology remain poorly understood. This study investigates how tebufenozide modulates gut immunity, microbial homeostasis, and antiviral defense mechanisms in H. armigera larvae. Using RT-qPCR, we analyzed the expression of key immune genes following exposure to lethal (LC₅₀) and sublethal (LC₁₀, LC₂₅) concentrations of tebufenozide. Our results demonstrate that tebufenozide induced the IMD pathway through upregulating Relish and PGRP-LC while suppressing PGRP-LB, leading to increased expression of antimicrobial peptides, Gallerimycin, Gloverin, Attacin and Defensin. Additionally, tebufenozide altered reactive oxygen species (ROS) dynamics by enhancing DUOX and SOD expression, resulted in decreased gut bacterial load. Additionally, tebufenozide enhanced antiviral defenses by upregulating RNAi pathway genes (Dicer1, Ago1, Dicer2, Ago2) and apoptosis-related genes (Caspase1, Caspase5), while downregulating the apoptosis inhibitor, Survivin. Consequently, viral titers of Helicoverpa armigera nucleopolyhedrovirus (HaNPV) were significantly lower in the treated larvae compared to the controls. These findings reveal that tebufenozide exerts immunomodulatory effects beyond molting disruption, influencing gut immunity, microbiota titer, and antiviral responses. This study highlights the broader physiological impacts of ecdysone agonists and their potential implications for integrated pest management strategies combining chemical and microbial agents.

昆虫生长调节剂虫酰肼是一种蜕皮激素激动剂，被广泛用于通过破坏棉铃虫的蜕皮和发育来控制棉铃虫。然而，它对昆虫生理的其他影响仍然知之甚少。本研究探讨了虫酰肼如何调节棉铃虫幼虫的肠道免疫、微生物稳态和抗病毒防御机制。使用RT-qPCR，我们分析了暴露于致命（LC₅₀）和亚致命（LC₁₀，LC₂₅）浓度的虫酰肼后关键免疫基因的表达。我们的研究结果表明，tebufenozide通过上调趣味和PGRP-LC而抑制PGRP-LB诱导IMD通路，导致抗菌肽、Gallerimycin、Gloverin、Attacin和Defensin的表达增加。此外，虫酰肼通过增强DUOX和SOD表达改变活性氧（ROS）动力学，导致肠道细菌负荷降低。此外，tebufenozide通过上调RNAi途径基因（Dicer1, Ago1, Dicer2, Ago2）和凋亡相关基因（Caspase1, Caspase5），同时下调凋亡抑制剂Survivin来增强抗病毒防御。结果表明，处理后的棉铃虫核多角体病毒（HaNPV）滴度明显低于对照。这些发现表明，除破坏换毛外，醚虫肼还具有免疫调节作用，影响肠道免疫、微生物群滴度和抗病毒反应。这项研究强调了蜕皮激素激动剂更广泛的生理影响及其对化学和微生物制剂相结合的综合害虫管理策略的潜在影响。

{"title":"Beyond molting disruption: Tebufenozide modifies gut immunity and antiviral responses in Helicoverpa armigera (Noctuidae)","authors":"Marzieh Attarianfar , Azam Mikani , Mohammad Mehrabadi","doi":"10.1016/j.cbpc.2026.110455","DOIUrl":"10.1016/j.cbpc.2026.110455","url":null,"abstract":"<div><div>The insect growth regulator tebufenozide, an ecdysone agonist, is widely used to control <em>Helicoverpa armigera</em> through disrupting molting and development. However, its other effects on the insect physiology remain poorly understood. This study investigates how tebufenozide modulates gut immunity, microbial homeostasis, and antiviral defense mechanisms in <em>H. armigera</em> larvae. Using RT-qPCR, we analyzed the expression of key immune genes following exposure to lethal (LC₅₀) and sublethal (LC₁₀, LC₂₅) concentrations of tebufenozide. Our results demonstrate that tebufenozide induced the IMD pathway through upregulating <em>Relish</em> and <em>PGRP-LC</em> while suppressing <em>PGRP-LB</em>, leading to increased expression of antimicrobial peptides, <em>Gallerimycin</em>, <em>Gloverin, Attacin</em> and <em>Defensin</em>. Additionally, tebufenozide altered reactive oxygen species (ROS) dynamics by enhancing <em>DUOX</em> and <em>SOD</em> expression, resulted in decreased gut bacterial load. Additionally, tebufenozide enhanced antiviral defenses by upregulating RNAi pathway genes (<em>Dicer1</em>, <em>Ago1</em>, <em>Dicer2</em>, <em>Ago2</em>) and apoptosis-related genes (<em>Caspase1</em>, <em>Caspase5</em>), while downregulating the apoptosis inhibitor, <em>Survivin</em>. Consequently, viral titers of <em>Helicoverpa armigera</em> nucleopolyhedrovirus (HaNPV) were significantly lower in the treated larvae compared to the controls. These findings reveal that tebufenozide exerts immunomodulatory effects beyond molting disruption, influencing gut immunity, microbiota titer, and antiviral responses. This study highlights the broader physiological impacts of ecdysone agonists and their potential implications for integrated pest management strategies combining chemical and microbial agents<strong>.</strong></div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"303 ","pages":"Article 110455"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984567","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}

引用次数: 0

6PPD impairs liver growth through inflammatory pathways: Insights from zebrafish and human cell models ppd通过炎症途径损害肝脏生长：来自斑马鱼和人类细胞模型的见解

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 : 2026-04-01 Epub Date: 2026-01-10 DOI: 10.1016/j.cbpc.2026.110454

Mengzhu Lv , Zheng Lu , Xiaoyu Mao , Jiangtao Huang , Qianqian Zheng , Dashuang Mo , Liping Shu

N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD), a widespread tire-derived contaminant, has drawn increasing concern for its environmental persistence and toxicity. However, its specific effects on early liver development remain poorly understood. In this study, we investigated the hepatotoxicity of 6PPD using zebrafish larvae and human L02 hepatocyte models. A novel exposure strategy was employed, initiating 6PPD treatment at 48 h post-fertilization, after liver budding, to minimize interference from early-stage developmental defects. 6PPD exposure led to a marked reduction in liver size without obvious morphological abnormalities, alongside downregulation of hepatocyte marker genes. Importantly, liver growth gradually recovered after 6PPD removal, suggesting acute and reversible toxicity. Mechanistically, 6PPD induced DNA damage and apoptosis in hepatocytes, as evidenced by elevated γ-H2AX, baxa, and casp3a expression, while hepatocyte proliferation remained unaffected. Transcriptomic and qPCR analyses revealed activation of inflammatory pathways and increased macrophage infiltration. Co-treatment with the anti-inflammatory agent dexamethasone rescued liver size and reduced DNA damage, indicating inflammation as a key mediator of 6PPD-induced toxicity. Similarly, 6PPD exposure in human hepatocytes reduced viability and increased apoptotic markers, which were alleviated by dexamethasone. These results demonstrate that 6PPD causes acute, inflammation-mediated liver toxicity during embryogenesis, with conserved mechanisms across species.

N-（1,3-二甲基丁基）-N'-苯基-对苯二胺（6PPD）是一种广泛存在的轮胎源污染物，其环境持久性和毒性已引起越来越多的关注。然而，它对早期肝脏发育的具体影响仍然知之甚少。本研究采用斑马鱼幼鱼和人L02肝细胞模型研究6PPD的肝毒性。采用了一种新的暴露策略，在受精后48 h，肝脏出芽后开始6PPD治疗，以尽量减少早期发育缺陷的干扰。6PPD暴露导致肝脏大小明显减小，但没有明显的形态学异常，同时肝细胞标记基因下调。重要的是，去除6PPD后，肝脏生长逐渐恢复，表明毒性是急性和可逆的。在机制上，6PPD诱导肝细胞DNA损伤和凋亡，γ-H2AX、baxa和casp3a表达升高，而肝细胞增殖未受影响。转录组学和qPCR分析显示炎症通路激活和巨噬细胞浸润增加。与抗炎药地塞米松联合治疗可挽救肝脏大小并减少DNA损伤，表明炎症是6ppd诱导毒性的关键介质。同样，6PPD暴露在人肝细胞中会降低细胞活力，增加凋亡标记物，地塞米松可以缓解这种情况。这些结果表明，6PPD在胚胎发生过程中引起急性炎症介导的肝毒性，其机制在物种间是保守的。

{"title":"6PPD impairs liver growth through inflammatory pathways: Insights from zebrafish and human cell models","authors":"Mengzhu Lv , Zheng Lu , Xiaoyu Mao , Jiangtao Huang , Qianqian Zheng , Dashuang Mo , Liping Shu","doi":"10.1016/j.cbpc.2026.110454","DOIUrl":"10.1016/j.cbpc.2026.110454","url":null,"abstract":"<div><div>N-(1,3-dimethylbutyl)-<em>N</em>′-phenyl-<em>p</em>-phenylenediamine (6PPD), a widespread tire-derived contaminant, has drawn increasing concern for its environmental persistence and toxicity. However, its specific effects on early liver development remain poorly understood. In this study, we investigated the hepatotoxicity of 6PPD using zebrafish larvae and human L02 hepatocyte models. A novel exposure strategy was employed, initiating 6PPD treatment at 48 h post-fertilization, after liver budding, to minimize interference from early-stage developmental defects. 6PPD exposure led to a marked reduction in liver size without obvious morphological abnormalities, alongside downregulation of hepatocyte marker genes. Importantly, liver growth gradually recovered after 6PPD removal, suggesting acute and reversible toxicity. Mechanistically, 6PPD induced DNA damage and apoptosis in hepatocytes, as evidenced by elevated γ-H2AX, <em>baxa</em>, and <em>casp3a</em> expression, while hepatocyte proliferation remained unaffected. Transcriptomic and qPCR analyses revealed activation of inflammatory pathways and increased macrophage infiltration. Co-treatment with the anti-inflammatory agent dexamethasone rescued liver size and reduced DNA damage, indicating inflammation as a key mediator of 6PPD-induced toxicity. Similarly, 6PPD exposure in human hepatocytes reduced viability and increased apoptotic markers, which were alleviated by dexamethasone. These results demonstrate that 6PPD causes acute, inflammation-mediated liver toxicity during embryogenesis, with conserved mechanisms across species.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"302 ","pages":"Article 110454"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958644","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}

引用次数: 0

Effects of short-term exposure to ferrous sulfate on bioaccumulation, oxidative stress biomarkers, immunity, and intestinal microbiota in Litopenaeus vannamei 短期暴露于硫酸亚铁对凡纳滨对虾生物积累、氧化应激生物标志物、免疫和肠道微生物群的影响

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 : 2026-04-01 Epub Date: 2026-01-05 DOI: 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.

重金属在水生环境中的积累对水产养殖构成严重威胁，其中铁（Fe）是工业和农业废水中最普遍的污染物之一。本研究评价了硫酸铁（FeSO₄）对凡纳滨对虾（Litopenaeus vannamei）的急性毒性和机理影响。急性毒性试验确定了Fe的96小时中位致死浓度（LC₅0）为2.52 mg/L，在0、24、48、72和96小时的暴露间隔内确定，标称浓度范围为0.2、1.0、5.0、25.0、125.0和625.0 mg/L。对照虾未发生死亡，而死亡率随着FeSO 4浓度和暴露时间的增加而逐渐增加。FeSO 4暴露导致肝胰腺和肌肉中显著的铁积累，伴随活性氧和丙二醛的升高，以及关键的抗氧化和免疫酶的抑制；超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和溶菌酶（LZM）。转录分析显示，应激蛋白（HSP70、HSP90、GSH-Px）、凋亡调节因子（caspase-3、p53）和免疫效应因子（金属硫蛋白）的表达强烈上调，而铁蛋白的表达下降，表明铁稳态被破坏。微生物群测序显示出明显的生态失调：对照虾保持平衡的共生类群，而铁暴露组则富含应激耐受性和机会性属，如希瓦氏菌和弧菌。功能预测（Tax4Fun）显示，铁暴露增强了外源生物降解、免疫疾病和细胞死亡相关途径，而与能量、氨基酸和碳水化合物代谢以及神经系统相关的功能相对下调。总的来说，FeSO 4暴露会损害抗氧化防御，引发细胞凋亡，诱导肠道生态失调，对水产养殖健康管理和环境风险评估具有重要意义。

{"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":"2026-04-01","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}

引用次数: 0

The effect of cypermethrin on neural tube development in the early stage of chick embryos 氯氰菊酯对早期鸡胚神经管发育的影响。

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 : 2026-04-01 Epub Date: 2026-01-18 DOI: 10.1016/j.cbpc.2026.110461

Yunus Emre Kundakci , Abdulkadir Bilir , Tolga Ertekin , Fatma Firat , Evrim Suna Arikan Soylemez

Cypermethrin, a type II pyrethroid insecticide, is widely used worldwide, but its potential teratogenicity remains a cause for concern. The present study aimed to investigate the dose-dependent effects of cypermethrin on neural tube development in early-stage chick embryos. Specific pathogen-free fertilized eggs (n = 125) were divided into five groups and treated subblastodermally at the 28th hour of incubation with saline (control) or cypermethrin at 0.01, 0.1, 1, or 10 ppm. The embryos were dissected after 48 h and evaluated for morphological, immunohistochemical, and genetic findings. Morphological analysis revealed a significant increase in open neural tube frequency, reduced crown–rump length, and decreased somite number at 1 and 10 ppm (p < 0.05). Immunohistochemical findings showed a dose-dependent increase in Caspase 3 and TUNEL indices, accompanied by a significant reduction in PCNA at higher concentrations (p < 0.001). Gene expression analysis revealed a consistent downregulation of transcription factor AP-2 (TFAP2) at all doses (p < 0.001), a non-significant alteration in brain and reproductive organ-expressed protein (BRE) (p > 0.05), and a significant upregulation of T-box transcription factor 18 (TBX18) at 10 ppm (p < 0.001). In conclusion, cypermethrin exposure during post-gastrulation impairs neural tube closure in chick embryos through enhanced apoptosis, reduced proliferation, and transcriptional dysregulation. These findings provide experimental evidence of the embryotoxic potential of pyrethroids and emphasize the need for stricter regulation of pesticide use to minimize developmental risks.

氯氰菊酯是一种II型拟除虫菊酯杀虫剂，在世界范围内广泛使用，但其潜在的致畸性仍然令人担忧。本研究旨在探讨氯氰菊酯对早期鸡胚神经管发育的剂量依赖性。将特异性无病原体受精卵（n = 125）分为5组，孵育28 h后分别用生理盐水（对照）或浓度分别为0.01、0.1、1、10 ppm的氯氰菊酯处理。胚胎在48 h后解剖，并对形态学、免疫组织化学和遗传学结果进行评估。形态学分析显示，在1和10 ppm （p  0.05）下，开放神经管频率显著增加，冠臀长度减少，体体数量减少（p  0.05）；在10 ppm （p 0.05）下，T-box转录因子18 （TBX18）显著上调（p 0.05）

{"title":"The effect of cypermethrin on neural tube development in the early stage of chick embryos","authors":"Yunus Emre Kundakci , Abdulkadir Bilir , Tolga Ertekin , Fatma Firat , Evrim Suna Arikan Soylemez","doi":"10.1016/j.cbpc.2026.110461","DOIUrl":"10.1016/j.cbpc.2026.110461","url":null,"abstract":"<div><div>Cypermethrin, a type II pyrethroid insecticide, is widely used worldwide, but its potential teratogenicity remains a cause for concern. The present study aimed to investigate the dose-dependent effects of cypermethrin on neural tube development in early-stage chick embryos. Specific pathogen-free fertilized eggs (<em>n</em> = 125) were divided into five groups and treated subblastodermally at the 28th hour of incubation with saline (control) or cypermethrin at 0.01, 0.1, 1, or 10 ppm. The embryos were dissected after 48 h and evaluated for morphological, immunohistochemical, and genetic findings. Morphological analysis revealed a significant increase in open neural tube frequency, reduced crown–rump length, and decreased somite number at 1 and 10 ppm (<em>p</em> < 0.05). Immunohistochemical findings showed a dose-dependent increase in Caspase 3 and TUNEL indices, accompanied by a significant reduction in PCNA at higher concentrations (<em>p</em> < 0.001). Gene expression analysis revealed a consistent downregulation of transcription factor AP-2 (TFAP2) at all doses (p < 0.001), a non-significant alteration in brain and reproductive organ-expressed protein (BRE) (<em>p</em> > 0.05), and a significant upregulation of T-box transcription factor 18 (TBX18) at 10 ppm (<em>p</em> < 0.001). In conclusion, cypermethrin exposure during post-gastrulation impairs neural tube closure in chick embryos through enhanced apoptosis, reduced proliferation, and transcriptional dysregulation. These findings provide experimental evidence of the embryotoxic potential of pyrethroids and emphasize the need for stricter regulation of pesticide use to minimize developmental risks.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"302 ","pages":"Article 110461"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146009090","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}

引用次数: 0