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

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 : 2026-01-23 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":"2026-01-23","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

Metabolomic insights into gut–brain axis dysregulation under unpredictable chronic stress in zebrafish 斑马鱼在不可预测的慢性应激下肠-脑轴失调的代谢组学见解。

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 : 2026-01-19 DOI: 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.

越来越多的证据表明，抑郁症与肠脑轴的紊乱密切相关。虽然啮齿类动物模型目前被广泛应用于抑郁症病理生理研究，但斑马鱼（Danio rerio）已成为一种有价值和有前途的替代模型物种。本研究在不可预测的慢性应激（UCS）斑马鱼模型中检测了与行为改变相关的神经内分泌和神经化学标志物的变化。经过14天的UCS程序，进行了开放场测试（OFT）、社会互动测试（SIT）和光暗测试（LDT）。全身皮质醇和IL-1β水平，以及大脑和肠道组织的代谢组学分析，用于神经内分泌和神经化学评估。观察到抑郁样行为，如不活动时间增加（P = 0.0009）和社交互动受损（P = 0.0306），同时皮质醇水平升高(P

{"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":"2026-01-19","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}

引用次数: 0

Toxicity and transcriptome sequencing analyses of Daphnia magna under multi-walled carbon nanotubes (MWCNTs) stress 多壁碳纳米管（MWCNTs）胁迫下大水蚤的毒性和转录组测序分析。

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

Comparative Biochemistry and Physiology C-toxicology & Pharmacology

Pub Date : 2026-01-19 DOI: 10.1016/j.cbpc.2026.110460

Jiaqi Shen , Zhenyang Zhang , Xudong Zheng , Pinpin Lv , Yong Huang , Xiaochan Gao

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.

近年来，随着动力电池工业的快速发展，碳纳米管的潜在污染问题引起了人们的高度关注。本研究研究了多壁碳纳米管（MWCNTs）对浮游生物模式生物大水蚤（Daphnia magna）抗氧化能力、消化能力和转录组的毒性。D. magna个体暴露于不同浓度（0、0.53 mg/L和5.3 mg/L）的MWCNTs 48 h。结果表明，5.3 mg/L MWCNTs诱导了明显的氧化应激，丙二醛含量显著升高，超氧化物歧化酶、过氧化氢酶和谷胱甘肽活性显著降低。与对照组相比，5.3 mg/ l暴露组的消化酶活性明显降低，包括脂肪酶活性、胰蛋白酶活性和淀粉酶活性。KEGG功能注释分析显示，两种浓度的MWCNTs都干扰了两条途径，包括细胞色素P450对外源药物的代谢和脂肪酸延伸信号通路。然而，5.3 mg/L mwcnts暴露组的蛋白质消化和吸收途径受到干扰，而0.53 mg/L mwcnts暴露组没有受到干扰。总之，我们推断氧化损伤、解毒功能损害以及蛋白质代谢和脂质代谢紊乱与碳纳米管对D. magna的毒性有关。

{"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":"2026-01-19","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}

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 : 2026-01-18 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":"2026-01-18","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

Effects of lighting technologies on the physiology of a marine diatom, Cocconeis scutellum var. parva (Bacillariophyceae): 2. production of antioxidants and other bioactive compounds 光照技术对海洋硅藻Cocconeis scutellum var. parva生理的影响（硅藻科）：2。生产抗氧化剂和其他生物活性化合物

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 : 2026-01-14 DOI: 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":"2026-01-14","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}

引用次数: 0

Multigenerational effects of selected environmental contaminants in fishes: A comprehensive review 综述：选定的环境污染物对鱼类的多代影响：一个全面的综述。

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 : 2026-01-13 DOI: 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.

水生生态系统中普遍存在的环境污染物引起了人们对其对水生生物，特别是鱼类的长期影响的重大关切。虽然生态毒理学研究传统上侧重于单代或单生命阶段的暴露，但这种方法可能低估或高估了人口水平的后果。这篇综述批判性地评估了目前关于鱼类中传统和新出现的污染物的多代影响的知识状况。该研究包括五大污染物类别：农药、药品和个人护理产品（PPCPs）、金属和类金属、微塑料和增塑剂、全氟烷基和多氟烷基物质（PFASs）。大多数多代研究都是在淡水物种上进行的，包括Danio rerio， Oryzias latipes, Oryzias melastigma, Oncorhynchus mykiss, Menidia beryllina, Nothobranchius furzeri， Pimephales promelas和parisgurnus dabryanus，突出了海洋鱼类的研究空白。研究结果一致表明，几代人暴露于这些污染物会导致发育、行为、生殖和神经发育障碍，这可能会降低生殖成功率、人口增长和整体健康。此外，新出现的证据表明，表观遗传修饰，如DNA甲基化和组蛋白改变，是这些多代效应的潜在机制。值得注意的是，我们的综述发现了研究之间相当大的差异，一些污染物表现出明显的多代毒性，而另一些则显示出有限或不一致的结果。鉴于全球对水生污染及其对生物多样性、粮食安全和公众健康的深远影响的日益关注，本综述强调了将多代终点纳入生态风险评估的迫切需要。

{"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":"2026-01-13","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}

引用次数: 0

IGF-1/AKT signaling attenuates arsenic-induced neuronal apoptosis and DNA fragmentation IGF-1/AKT信号通路减弱砷诱导的神经元凋亡和DNA断裂

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 : 2026-01-12 DOI: 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.

慢性砷暴露是神经毒性的主要环境原因，与氧化应激和细胞凋亡有关。虽然它的毒性已经确定，但保护策略是有限的。胰岛素样生长因子-1 （IGF-1）是一种关键的神经营养因子，但其对抗砷诱导的神经元凋亡和DNA断裂的潜力仍未得到充分研究。研究了IGF-1对人SH-SY5Y神经母细胞瘤细胞亚砷酸钠（NaAsO₂）的神经保护作用。分化细胞用于研究IGF-1/AKT信号，未分化细胞用于研究凋亡。细胞在有或没有IGF-1处理的情况下暴露于NaAsO₂。Western blot检测AKT在Thr308和Ser473位点的磷酸化状态。通过亚g1细胞群的流式细胞术分析和关键凋亡标记物的免疫印迹分析来评估细胞凋亡，包括裂解的caspase-3、裂解的PARP、p53和Bcl-2。砷暴露显著抑制AKT磷酸化并诱导浓度依赖性凋亡，p53、裂解caspase-3、PARP裂解增加，Bcl-2代偿性增加。用IGF-1治疗可显著减弱这些效应。IGF-1恢复AKT信号，减少促凋亡标志物（p53, cleaved caspase-3），减少PARP切割，并显著减少凋亡细胞死亡和DNA断裂（亚g1群体）。在IGF-1治疗后观察到Bcl-2的减少表明凋亡平衡的恢复。这些发现提供了新的证据，表明IGF-1通过重新激活PI3K/AKT通路，对砷诱导的神经细胞凋亡和DNA断裂具有保护作用。这种再激活重新平衡了凋亡调节因子并抑制了p53介导的细胞凋亡。这些发现强调了IGF-1信号作为砷相关神经元损伤的一个有希望的治疗靶点，值得进一步的体内研究。

{"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":"2026-01-12","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}

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 : 2026-01-12 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":"2026-01-12","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 : 2026-01-10 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":"2026-01-10","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

Selenium regulates pyroptosis through the ROS-mtDNA-cGAS-STING axis to alleviate trimethyltin chloride-induced inflammation in chicken kidneys 硒通过ROS-mtDNA-cGAS-STING轴调控鸡肾脏焦亡，减轻三甲基锡氯致炎症。

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 : 2026-01-10 DOI: 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.

三甲基氯化锡（TMT）是一种剧毒且普遍存在于环境中的有机锡化合物。硒（Se）通过减轻氧化应激来减轻毒素诱导的损伤，而线粒体DNA （mtDNA）泄漏通过mtDNA- cgas - sting途径激活焦亡和炎症。然而，硒通过ros - mtdna - cgas - sting介导的焦亡拮抗tmt诱导的鸡肾炎症的确切机制尚不清楚。我们建立了鸡TMT模型（10 μg kg-1灌胃） ± 富硒日粮（2 mg kg-1）。采用原代鸡胚肾（CEK）细胞进行体外验证。体内和体外数据显示，TMT抑制抗氧化剂（CAT, GSH-Px， SOD, T-AOC），升高H2O2/MDA，并引起过量的ROS。TMT还会使线粒体膜电位去极化（ΔΨm），升高线粒体ROS (mtROS)，诱导mtDNA释放，扰乱线粒体动力学，最终导致严重的线粒体功能障碍。胞质mtDNA激活cGAS-STING通路，上调关键信号分子，增加焦亡标志物（Caspase1、NLRP3、GSDMD、IL-18）和促炎因子（TNF-α、ASC、IL-1β、IL-6）。硒的补充逆转了这些变化。重要的是，硒介导的保护作用被氧化应激诱导剂血氨酸、cGAS-STING激动剂STING-Agonist 12或焦腐激活剂尼日利亚菌素所消除。总之，我们的研究结果表明，硒通过减少ROS、保持线粒体稳态、防止mtDNA泄漏和抑制cGAS-STING途径来减轻tmt诱导的肾焦亡和炎症。这些发现不仅阐明了TMT肾毒性的分子基础，而且支持Na2SeO3作为TMT所致肾损伤的候选治疗药物。

{"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":"2026-01-10","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}

引用次数: 0