{"title":"Combined effects of high-fat diet feeding and Streptococcus agalactiae infection on lipid metabolism, antioxidant status, and immune response in tilapia (Oreochromis niloticus).","authors":"Rui Jia, Yiran Hou, Linjun Zhou, Chengfeng Zhang, Bing Li, Jian Zhu","doi":"10.1016/j.cbpc.2025.110321","DOIUrl":"10.1016/j.cbpc.2025.110321","url":null,"abstract":"<p><p>High-fat diet (HFD) and Streptococcus agalactiae are common pathogenic factors affecting tilapia health, yet their combined effects and underlying mechanisms are not well understood. To address this, we conducted a comprehensive evaluation of the potential response mechanisms in tilapia subjected to both factors. Tilapia were fed normal (NC) or high-fat diet (HFD) for 90 days, then challenged with S. agalactiae. At 48 h post-infection, blood, liver, and spleen samples were collected for biochemical parameter analysis and gene expression profiling. The results indicated that the combined treatment upregulated the expression of peroxisome proliferator-activated receptor α (pparα) and fatty acid transport protein 1 (fatp1). Concurrently, it increased 3-hydroxy-3-methylglutaryl-CoA reductase (hmgcr) expression, while decreasing cholesterol 7α-hydroxylase (cyp7a1) expression compared to HFD alone. Antioxidant status analysis revealed that the combined treatment decreased glutathione (GSH) content, total antioxidant capacity (T-AOC), and mRNA levels of nuclear factor erythroid 2-related factor 2 (nrf2), NAD(P)H quinone dehydrogenase 1 (nqo1), and glutathione peroxidase 3 (gpx3). Intriguingly, while both individual stressors upregulated inflammatory and immune-related genes, their combination suppressed interleukin-1β (il-1β), il-8, and immunoglobulin M (igm) expression compared to infection alone. The apoptotic response triggered by S. agalactiae infection, characterized by elevated caspase-3 (cas3), cas9, and cytochrome c (cytc), was inhibited in the liver of combined treatment group. Moreover, all experimental groups showed elevated expression of endoplasmic reticulum stress-related genes: inositol-requiring enzyme 1 (ire1), eukaryotic translation initiation factor 2 alpha kinase 3 (eif2ak3), activating transcription factor 6 (atf6), and binding immunoglobulin protein (bip). These findings collectively demonstrated that HFD exacerbated the pathogenic effects of S. agalactiae through multiple mechanisms, including metabolic dysregulation, oxidative stress potentiation, and complex immunomodulation. Furthermore, the Nrf2 and NF-kB signaling pathways may be implicated in mediating these adverse effects.</p>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":" ","pages":"110321"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811914","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}
Kang Chen, Zheng He, Peiyu Xie, Yihui Jia, Hong Liu, Zexia Gao, Huanling Wang
{"title":"Mitochondrial function and energy metabolism response of Megalobrama amblycephala under heat and hypoxia.","authors":"Kang Chen, Zheng He, Peiyu Xie, Yihui Jia, Hong Liu, Zexia Gao, Huanling Wang","doi":"10.1016/j.cbpc.2025.110306","DOIUrl":"10.1016/j.cbpc.2025.110306","url":null,"abstract":"<p><p>Ongoing global climate change and anthropogenic activities are increasingly subjecting aquatic animals to heat and hypoxia stress. These environmental perturbations can profoundly impact mitochondrial function and energy metabolism. The current study aimed to delineate the adaptive mechanisms of mitochondrial dynamics and energy metabolism in the blunt snout bream (Megalobrama amblycephala) under three experimental conditions: heat stress (HT group, 35 °C of temperature), hypoxia stress (LO group, 2 mg/L of dissolved oxygen), and combined heat plus hypoxia stress (HL group, 35 °C and 2 mg/L). The results demonstrated that heat and/or hypoxia stresses damaged mitochondrial structure and disrupted fusion-fission balance. The activities of key TCA cycle enzymes (e.g. SDH, CS) were significantly decreased. Conversely, energy metabolism was regulated through an increased AMP/ATP ratio and activation of AMPKα1/AMPKα2 proteins. The expression of glycolytic enzymes (PK, PFK, HK and LDH) was up-regulated. However, heat and/or hypoxia stresses resulted in severe consumption of serum glucose and liver glycogen, with the most pronounced consumption in the HL group. Other saccharides such as mannose and lactose were also significantly reduced in HT and HL groups. The decomposition and metabolism of amino acids was an important auxiliary mechanism. Regarding lipid metabolism, the expression of lipolysis and lipogenesis related genes was down-regulated, while glycerophospholipids accumulation contributed to maintaining membrane integrity. These findings benefit the understanding of environmental adaptive characteristics in aquatic animals and provide effective strategies for aquaculture management.</p>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":" ","pages":"110306"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788452","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}
Amanda Ameyaa-Sakyi, Todd R Harris, Colleen E Clarke, David R McMullin, Kacy L Gordon, David Sherwood, Jessica H Hartman, Amy A Rand
{"title":"Human mitochondrial CYP2E1-mediated styrene metabolism increases oxidative stress and impairs antioxidant rescue in Caenorhabditis elegans.","authors":"Amanda Ameyaa-Sakyi, Todd R Harris, Colleen E Clarke, David R McMullin, Kacy L Gordon, David Sherwood, Jessica H Hartman, Amy A Rand","doi":"10.1016/j.cbpc.2025.110319","DOIUrl":"10.1016/j.cbpc.2025.110319","url":null,"abstract":"<p><p>Styrene is an environmental toxicant metabolized by cytochrome P450 2E1 (CYP2E1) to styrene oxide, a reactive intermediate product linked to oxidative stress. While the role of CYP2E1 in xenobiotic metabolism is well established, the influence of subcellular enzyme localization on styrene-induced toxicity remains unclear. This study used transgenic Caenorhabditis elegans (C. elegans) strains expressing CYP2E1 in different compartments, mitochondrial-derived (mtCYP2E1) and endoplasmic reticulum-derived (erCYP2E1), to investigate the impact of CYP2E1-mediated styrene metabolism on survival and oxidative stress. CYP2E1 containing C. elegans strains were also compared to a wildtype strain (N2) lacking CYP2E1. Styrene exposure significantly decreased survival across all strains. Antioxidant rescue assays revealed that Trolox and N-acetyl cysteine (NAC) improved survival in the N2 and erCYP2E1 C. elegans strains but not in mtCYP2E1, indicating a distinct oxidative stress mechanism in mitochondrial CYP2E1 metabolism. Fluorescent microscopy confirmed that ROS levels increased with styrene exposure, particularly in mtCYP2E1 C. elegans, where ROS levels were up to two-fold higher than in other strains. GC-MS analysis detected elevated styrene glycol production in styrene-exposed mtCYP2E1 C. elegans relative to N2 and erCYP2E1 strains. Given styrene oxide is a known cytotoxic intermediate, its accumulation in the mtCYP2E1 strain likely contributes to the observed oxidative stress and decreased survival. These findings suggest that CYP2E1 subcellular localization influences styrene metabolism and toxicity, with mitochondrial CYP2E1 potentially promoting higher oxidative stress and reduced detoxification efficiency. A better understanding of these mechanisms could provide insight into xenobiotic metabolism, environmental toxicology, and disease pathogenesis associated with CYP2E1-mediated oxidative stress.</p>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":" ","pages":"110319"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803825","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}
Juan Ignacio Bertucci, Angie Blanco Osorio, Leticia Vidal-Liñán, Juan Bellas
{"title":"Molecular markers of stress in the sea urchin embryo test: Analysing the effect of climate change and pollutant mixtures on Paracentrotus lividus larvae.","authors":"Juan Ignacio Bertucci, Angie Blanco Osorio, Leticia Vidal-Liñán, Juan Bellas","doi":"10.1016/j.cbpc.2025.110320","DOIUrl":"10.1016/j.cbpc.2025.110320","url":null,"abstract":"<p><p>Climate change and pollution represent critical stressors for marine ecosystems, particularly for calcifying organisms such as the sea urchin Paracentrotus lividus. This study examines the combined effects of ocean acidification (OA), ocean warming (OW), and microplastics (MP) loaded with chlorpyrifos (CPF), a broad-spectrum organophosphate insecticide, on sea urchin larvae, evaluating growth and molecular endpoints. Experimental treatments simulated future ocean conditions predicted for 2100, exposing larvae to varying temperature and pH levels, alongside CPF-contaminated MP. RNA sequencing (RNA-seq) was utilized to assess gene expression changes, revealing significant transcriptional shifts in metabolic, cellular, and developmental pathways. Morphological responses showed reduced larval growth, exacerbated under OA and OW conditions. Molecular analyses identified key upregulated pathways associated with stress response, including nitrogen metabolism and extracellular matrix remodelling, while downregulated genes involved DNA stability, cell cycle regulation, and enzymatic activities. These findings suggest a dual compensatory and deleterious response to combined stressors. Notably, temperature acted as a modulator of stressor effects, amplifying oxidative stress and metabolic costs at higher temperatures. Potential biomarkers, such as genes involved in actin regulation and embryonic development, were identified, offering possible tools for early detection of environmental stress. This study highlights the compounded impacts of anthropogenic and climate-induced stressors on marine invertebrates, emphasizing the need for integrative molecular approaches in ecotoxicology. Our findings contribute to the understanding of organismal adaptation and vulnerability in the face of global climate change and pollution, informing conservation strategies for marine ecosystems.</p>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":" ","pages":"110320"},"PeriodicalIF":4.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803826","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}
{"title":"Effects of cypermethrin on the clams Ruditapes philippinarum (A. Adams & Reeve, 1850).","authors":"Lihua Qi, Chengang Hua, Zongqi Ye, Xu Shen, Yuefeng Cai, Xin Shen","doi":"10.1016/j.cbpc.2025.110366","DOIUrl":"https://doi.org/10.1016/j.cbpc.2025.110366","url":null,"abstract":"<p><p>Cypermethrin, highly toxic to aquatic life, impacts Ruditapes philippinarum (A. Adams & Reeve, 1850), an economically valuable species. Thus, studying its toxicity mechanism to R. philippinarum is crucial. In this research, R. philippinarum was exposed to 5000 ng/L cypermethrin and sampled on days 0, 1, 3, 6, 10, 15, and 21 to assess enzymatic activities and conduct transcriptome sequencing. The enzymatic activity results showed that cypermethrin could increase the activity of the ethoxyresorufin-O-deethylase (EROD), turn on the antioxidant defenses, cause an initial increase in total antioxidant capacity (T-AOC) and then a decrease, increase the activities of antioxidant enzymes catalase (CAT) and glutathione peroxidase (GPx), and inhibit superoxide dismutase (SOD). Furthermore, the contents of malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) increased in the body at 10, 15, and 21 days of exposure. Transcriptome sequencing was carried out to analyze the responses of cypermethrin stress for 1 day and 21 days. Differentially expressed genes (DEGs) were linked to detoxification metabolism and oxidative stress, according to Gene Ontology (GO) enrichment analysis. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis demonstrated that cypermethrin had toxic effects through key factors affecting detoxification metabolism, oxidative stress, immune response, and apoptosis-related pathways. This study gives insights into the harmful mechanism of cypermethrin stress on R. philippinarum, as well as a theoretical basis for assessing the ecological danger of cypermethrin in Chinese coastal waters.</p>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":" ","pages":"110366"},"PeriodicalIF":4.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228469","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}
{"title":"miR-23a modulates chlorantraniliprole susceptibility by targeting SfGSTs3 in Spodoptera frugiperda (Smith).","authors":"Fan-Bin Kong, Yong-Po Lv, Bai-Zhong Zhang, Meng-Yuan Zhang, Ling-Ling Cui, Ren-Jie Li, Dong-Mei Chen, Yu-Yang Peng, Run-Qiang Liu","doi":"10.1016/j.cbpc.2025.110367","DOIUrl":"https://doi.org/10.1016/j.cbpc.2025.110367","url":null,"abstract":"<p><p>The fall armyworm Spodoptera frugiperda (Smith) can damage many crops distributed worldwide, and chemical insecticide application is the main control strategy. However, the frequent application of insecticides can lead to severe insecticide resistance in S. frugiperda. Glutathione S-transferases (GSTs) play a critical role in insecticide resistance in pests. In this study, it was found that the expression of SfGSTs3 was significantly up-regulated after exposure to chlorantraniliprole. After injection of dsSfGSTs3, the susceptibility of chlorantraniliprole was improved, and microRNA-23a binding on 3'UTR of SfGSTs3 was found. Luciferase reporter assays revealed that the effects of miR-23a on SfGSTs3 expression were suppressed via this binding site in S. frugiperda. Injection of the miR-23a agomir significantly reduced SfGSTs3 expression, together with increased chlorantraniliprole susceptibility. In contrast, injection of the miR-23a antagomir significantly improved SfGSTs3 expression and thus decreased chlorantraniliprole susceptibility in the larvae of S. frugiperda. These findings provide a theoretical foundation for better understanding the posttranscriptional regulation of SfGSTs3 and can be used to further study the mechanism by which miRNAs regulate insecticide susceptibility in pests.</p>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":" ","pages":"110367"},"PeriodicalIF":4.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228452","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}
{"title":"Effects of bisphenol A on freshwater mussels: Insights into the protective mechanisms of selenium","authors":"Oumaima Abidi , Abdelhafidh Khazri , Rihab Belgacem , Tamara García-Barrera , Ezzeddine Mahmoudi , Mohamed Dellali","doi":"10.1016/j.cbpc.2025.110362","DOIUrl":"10.1016/j.cbpc.2025.110362","url":null,"abstract":"<div><div>Bisphenol A (BPA), a widespread environmental pollutant, is known for its endocrine-disrupting and pro-oxidant effects, posing serious risks to aquatic organisms. This study evaluated the impact of BPA on biochemical markers in the digestive gland of the freshwater mussel <em>Unio ravoisieri</em>, and assessed the potential protective role of selenium (Se), a trace element with antioxidant properties. Under laboratory conditions, mussels were exposed for 14 days to two BPA concentrations (C<sub>1</sub> = 10 μg/L and C<sub>2</sub> = 100 μg/L), either alone or combined with 100 μg/L Se. The enzymatic activity of acetylcholinesterase (AChE), catalase (CAT), and glutathione S-transferase (GST), along with the levels of malondialdehyde (MDA), reduced glutathione (GSH), and hydrogen peroxide (H₂O₂), were quantified as indicators of neurotoxicity and oxidative stress. BPA exposure led to a significant dose-dependent inhibition of AChE activity, indicating neurotoxicity, while GST activity increased, suggesting an upregulated detoxification response. An increase in CAT activity was observed at the lower BPA dose, while inhibition occurred at the higher dose. Importantly, BPA significantly GSH levels, indicating oxidative stress and impaired antioxidant and detoxification defenses. Additionally, BPA exposure at both 10 μg/L and 100 μg/L significantly elevated MDA and H₂O₂ levels, with a more pronounced increase observed at the higher dose (100 μg/L), confirming enhanced lipid peroxidation and reactive oxygen species (ROS). Notably, Se co-treatment mitigated these adverse effects by partially restoring AChE and CAT activities, normalizing GST responses, preserving GSH content, and reducing oxidative damage. These findings demonstrate the intertwined oxidative and detoxification responses of <em>U. ravoisieri</em> to BPA exposure and underscore the protective role of Se in counteracting BPA-induced toxicity. This study reinforces the utility of biochemical biomarkers in environmental monitoring and supports the potential use of Se in pollution mitigation strategies.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"299 ","pages":"Article 110362"},"PeriodicalIF":4.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155991","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}
Yue Li , Zihao Jiang , Zhuoshuo Zhou , Naitian Zhang , Ximing Cui , Xiaoyan Yu , Yanli Zhao , Zhong Wang , Jinlian Li , Dongmei Wu
{"title":"Differential toxic phenotypes and liver injury induced by Atractylenolides (I, II, and III): Insights from zebrafish (Danio rerio) models and network toxicology","authors":"Yue Li , Zihao Jiang , Zhuoshuo Zhou , Naitian Zhang , Ximing Cui , Xiaoyan Yu , Yanli Zhao , Zhong Wang , Jinlian Li , Dongmei Wu","doi":"10.1016/j.cbpc.2025.110365","DOIUrl":"10.1016/j.cbpc.2025.110365","url":null,"abstract":"<div><div>Atractylenolides (I, II, and III), active sesquiterpene lactones from <em>Atractylodes macrocephala</em> Koidz, exhibit diverse pharmacological activities but have been reported to impair drug-metabolizing enzymes and hepatocellular function. However, a comprehensive safety assessment of these compounds remains lacking. In this study, we investigated the developmental toxicity profile of Atractylenolides (I, II, and III) in zebrafish embryos, with a particular focus on hepatotoxicity and its underlying mechanisms. Exposure to Atractylenolides (I, II, and III) resulted in concentration-dependent mortality, with 96-h median lethal concentrations (LC₅₀) of 81.64 μM, 138.40 μM, and 151.90 μM, respectively. Atractylenolides (I, II) induced multiple developmental abnormalities, among which Atractylenolide-I uniquely led to neuronal developmental arrest and diminished locomotor activity. Importantly, Atractylenolides (I, II) exhibited marked hepatotoxicity, evidenced by liver shrinkage, reduced liver-specific fluorescence intensity, and elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). In contrast, exposure to Atractylenolide-III did not induce significant toxic effects. Network toxicology analysis revealed that cytochrome P450 (CYP450) metabolism and apoptosis were closely associated with Atractylenolides (I, II) induced hepatotoxicity. qRT-PCR analysis revealed that Atractylenolides (I, II) suppressed mRNA expression of key drug-metabolizing genes, including <em>cyp3c1</em> and <em>cyp3a65</em>. Simultaneously, Atractylenolides (I, II) downregulated genes associated with cell proliferation (<em>top2α</em>, <em>uhrf1</em>). Co-treatment with the hepatoprotective agent silybin partially reversed the liver injury and the alterations in drug metabolism gene expression induced by Atractylenolides (I, II). Collectively, our results provide important insights into the safety evaluation of Atractylenolides (I, II, and III).</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"299 ","pages":"Article 110365"},"PeriodicalIF":4.3,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148195","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}
Marwin Jafari , Jason T. Magnuson , Fabian Essfeld , Sebastian Eilebrecht , Katharina Brotzmann , Daniela M. Pampanin
{"title":"Amitriptyline and nortriptyline induce ocular toxicity in early life stage zebrafish (Danio rerio)","authors":"Marwin Jafari , Jason T. Magnuson , Fabian Essfeld , Sebastian Eilebrecht , Katharina Brotzmann , Daniela M. Pampanin","doi":"10.1016/j.cbpc.2025.110363","DOIUrl":"10.1016/j.cbpc.2025.110363","url":null,"abstract":"<div><div>The global use of antidepressants has steadily increased, raising concern to aquatic ecosystems due to the incomplete removal during wastewater treatment. Tricyclic antidepressants (TCAs) act on the neuronal system by inhibiting the reuptake of serotonin and norepinephrine. However, despite visual function being heavily dependent on the neuronal system, a knowledge gap remains regarding the ocular toxicity of TCAs. To bridge this knowledge gap, zebrafish (<em>Danio rerio</em>) embryos were exposed to sublethal test concentrations of amitriptyline (AMI, 0.3 to 300 μg/L nominal, 2.04 to 234 μg/L measured) and nortriptyline (NOR, 0.03 to 300 μg/L nominal, >0.107 to 20.7 μg/L measured), with the lowest test concentrations being environmentally relevant. Visual function was assessed with the optokinetic response assay, eye structure development was assessed histologically, and gene expression changes were analysed via transcriptomic profiling. Larval zebrafish (120 h post fertilization (hpf)) exposed to 4.99 and 234 μg/L of AMI exhibited a 26 % and 86 % decrease in the number of eye saccades respectively, with zebrafish exposed to 20.7 μg/L of NOR exhibiting a 65 % decrease. Histological analysis indicated a significant increase of the retinal pigment epithelium thickness after exposure to 234 μg/L of AMI and 20.7 μg/L of NOR. Transcriptomic analysis resulted in 1207 and 2742 differentially expressed genes across both AMI and NOR treatment groups respectively, including genes involved in vision, synaptic signaling, and neuronal development. These findings demonstrate that sublethal concentrations of AMI and NOR affect early life stage zebrafish visual development, which may be sensitive endpoint that could be incorporated into ecological risk assessments.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"299 ","pages":"Article 110363"},"PeriodicalIF":4.3,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148219","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}
{"title":"Endotoxin lipopolysaccharide challenge triggers gut microbiota dysbiosis and host immune remodeling in the tiger grouper Epinephelus fuscoguttatus","authors":"Yafei Duan , Yukai Yang , Ruijie Zhu , Meng Xiao","doi":"10.1016/j.cbpc.2025.110364","DOIUrl":"10.1016/j.cbpc.2025.110364","url":null,"abstract":"<div><div>Lipopolysaccharide (LPS) is a bacterial endotoxin that can trigger immune responses in aquatic animals. The gut microbiota is crucial for nutrient absorption and immune regulation in fish. In this study, the tiger grouper <em>Epinephelus fuscoguttatus</em> was selected as an animal model to investigate the effects of LPS challenge on the composition and function of gut microbiota and the gene transcriptional profiles of head kidney. The results showed that LPS challenge slightly increased gut microbial diversity indices (ACE, Simpson) and decreased Chao1 and Shannon indices; it also increased the abundances of Proteobacteria and harmful bacteria (<em>Vibrio</em>, <em>Pseudomonas</em>), while decreased those of Firmicutes, Actinobacteria and beneficial bacteria (<em>Collinsella</em>, <em>Romboutsia</em>) that produce short-chain fatty acids. The predicted carbohydrate and protein digestion/absorption functions of gut microbiota were significantly weakened. Additionally, LPS challenge induced 757 up- and 379 down-regulated genes in the head kidney, mainly involved in DNA replication, aminoacyl-tRNA biosynthesis and two-component system. Immune-related genes including pattern recognition receptors <em>TLR1</em>/<em>2</em> was up-regulated but <em>TLR3</em> was down-regulated; immune regulation (<em>PIgR</em>, <em>MHC2</em>), apoptosis (<em>Cytc</em>, <em>Casp3</em>, <em>BIRC5</em>), stress response (<em>HSP60/70/90</em>, <em>GRP94</em>, <em>Bip</em>, <em>HURP1</em>) and iron homeostasis (<em>Mfn1</em>, <em>TFR1</em>, <em>Hepc</em>) related genes were up-regulated; complement (<em>C1QL3</em>, <em>C1QBP</em>, <em>C7</em>), chemokines and their receptors (<em>LECT2</em>, <em>CXCR3/1/4</em>, <em>CCR2</em>) related genes showed disordered expression. Several bacterial genera groups, such as <em>Collinsella</em>, <em>Romboutsia</em>, <em>Phyllobacterium</em>, <em>Prevotella 9</em>, and <em>Prevotellaceae NK3B31</em>, were positively associated with the changes in host immune function. These findings demonstrated that LPS challenge induced the structural perturbations of gut microbiota, and disrupted the immune homeostasis of the head kidney of the grouper.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"299 ","pages":"Article 110364"},"PeriodicalIF":4.3,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148224","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}