Pub Date : 2025-10-10DOI: 10.1016/j.cbpc.2025.110368
Bence Ivánovics , Gyöngyi Gazsi , Zoltán K. Varga , Ádám Staszny , Eszter Váradi , Zsófia Varga , András Ács , Márta Tóth , Apolka Domokos , Márta Reining , Erna Vásárhelyi , Szilárd Póliska , Róbert Kovács , Ferenc Baska , Zoltán Filep , Attila Bácsi , Julianna Kobolák , Béla Urbányi , István Szabó , Tamás Müller , Zsolt Czimmerer
The emergence and spread of vector-borne diseases necessitate the increased use of insecticides, such as carbamates, raising concerns about their potential toxicological risks to non-target organisms, including humans. Bendiocarb, frequently applied in indoor spraying operations and detected in maternal and fetal circulation, warrants particular attention for its developmental toxicity. This study aimed to assess transcriptional and phenotypic effects of sublethal bendiocarb exposure at concentrations of 0.035, 0.2, 0.4, 0.75, and 1.5 mg/L, using zebrafish embryos, a vertebrate model for developmental toxicity testing. Our analyses revealed acetylcholinesterase inhibition-associated morphological and behavioral abnormalities, including reduced locomotor activity in response to both visual and tactile stimuli, as well as impaired non-associative learning. Transcriptomic analysis indicated activation of muscle, immune, and metabolic pathways, while neurodevelopmental, phototransduction, and cell proliferation processes were suppressed. Consistent with these molecular findings, structural damage was observed in the retina, skeletal muscle, and notochord. Furthermore, bendiocarb exposure disrupted neutrophil granulocyte distribution and impaired inflammatory responses. Altogether, our results provide new insights into the embryotoxic effects of bendiocarb, highlighting its potential to disrupt early vertebrate development. These findings provide mechanistic insight that may support more informed evaluations of potential public health risks associated with developmental exposure to carbamates.
{"title":"Carbamate insecticide bendiocarb induces complex embryotoxic effects, including morphological, behavioral, transcriptional, and immunological alterations in zebrafish","authors":"Bence Ivánovics , Gyöngyi Gazsi , Zoltán K. Varga , Ádám Staszny , Eszter Váradi , Zsófia Varga , András Ács , Márta Tóth , Apolka Domokos , Márta Reining , Erna Vásárhelyi , Szilárd Póliska , Róbert Kovács , Ferenc Baska , Zoltán Filep , Attila Bácsi , Julianna Kobolák , Béla Urbányi , István Szabó , Tamás Müller , Zsolt Czimmerer","doi":"10.1016/j.cbpc.2025.110368","DOIUrl":"10.1016/j.cbpc.2025.110368","url":null,"abstract":"<div><div>The emergence and spread of vector-borne diseases necessitate the increased use of insecticides, such as carbamates, raising concerns about their potential toxicological risks to non-target organisms, including humans. Bendiocarb, frequently applied in indoor spraying operations and detected in maternal and fetal circulation, warrants particular attention for its developmental toxicity. This study aimed to assess transcriptional and phenotypic effects of sublethal bendiocarb exposure at concentrations of 0.035, 0.2, 0.4, 0.75, and 1.5 mg/L, using zebrafish embryos, a vertebrate model for developmental toxicity testing. Our analyses revealed acetylcholinesterase inhibition-associated morphological and behavioral abnormalities, including reduced locomotor activity in response to both visual and tactile stimuli, as well as impaired non-associative learning. Transcriptomic analysis indicated activation of muscle, immune, and metabolic pathways, while neurodevelopmental, phototransduction, and cell proliferation processes were suppressed. Consistent with these molecular findings, structural damage was observed in the retina, skeletal muscle, and notochord. Furthermore, bendiocarb exposure disrupted neutrophil granulocyte distribution and impaired inflammatory responses. Altogether, our results provide new insights into the embryotoxic effects of bendiocarb, highlighting its potential to disrupt early vertebrate development. These findings provide mechanistic insight that may support more informed evaluations of potential public health risks associated with developmental exposure to carbamates.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"299 ","pages":"Article 110368"},"PeriodicalIF":4.3,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-02DOI: 10.1016/j.cbpc.2025.110366
Lihua Qi , Chengang Hua , Zongqi Ye , Xu Shen , Yuefeng Cai , Xin Shen
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.
{"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":"10.1016/j.cbpc.2025.110366","url":null,"abstract":"<div><div>Cypermethrin, highly toxic to aquatic life, impacts <em>Ruditapes philippinarum</em> (A. Adams & Reeve, 1850), an economically valuable species. Thus, studying its toxicity mechanism to <em>R. philippinarum</em> is crucial. In this research, <em>R. philippinarum</em> 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 <em>R. philippinarum</em>, as well as a theoretical basis for assessing the ecological danger of cypermethrin in Chinese coastal waters.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"299 ","pages":"Article 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}
Pub Date : 2025-10-02DOI: 10.1016/j.cbpc.2025.110367
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
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.
{"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":"10.1016/j.cbpc.2025.110367","url":null,"abstract":"<div><div>The fall armyworm <em>Spodoptera frugiperda</em> (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 <em>S. frugiperda</em>. 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 <em>SfGSTs3</em> expression were suppressed via this binding site in <em>S. frugiperda</em>. Injection of the miR-23a agomir significantly reduced <em>SfGSTs3</em> expression, together with increased chlorantraniliprole susceptibility. In contrast, injection of the miR-23a antagomir significantly improved <em>SfGSTs3</em> expression and thus decreased chlorantraniliprole susceptibility in the larvae of <em>S. frugiperda</em>. These findings provide a theoretical foundation for better understanding the posttranscriptional regulation of <em>SfGSTs3</em> and can be used to further study the mechanism by which miRNAs regulate insecticide susceptibility in pests.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"299 ","pages":"Article 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}
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 Unio ravoisieri, 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 (C1 = 10 μg/L and C2 = 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 U. ravoisieri 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.
{"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}
Pub Date : 2025-09-23DOI: 10.1016/j.cbpc.2025.110365
Yue Li , Zihao Jiang , Zhuoshuo Zhou , Naitian Zhang , Ximing Cui , Xiaoyan Yu , Yanli Zhao , Zhong Wang , Jinlian Li , Dongmei Wu
Atractylenolides (I, II, and III), active sesquiterpene lactones from Atractylodes macrocephala 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 cyp3c1 and cyp3a65. Simultaneously, Atractylenolides (I, II) downregulated genes associated with cell proliferation (top2α, uhrf1). 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).
{"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}
Pub Date : 2025-09-23DOI: 10.1016/j.cbpc.2025.110363
Marwin Jafari , Jason T. Magnuson , Fabian Essfeld , Sebastian Eilebrecht , Katharina Brotzmann , Daniela M. Pampanin
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 (Danio rerio) 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.
{"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}
Pub Date : 2025-09-23DOI: 10.1016/j.cbpc.2025.110364
Yafei Duan , Yukai Yang , Ruijie Zhu , Meng Xiao
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 Epinephelus fuscoguttatus 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 (Vibrio, Pseudomonas), while decreased those of Firmicutes, Actinobacteria and beneficial bacteria (Collinsella, Romboutsia) 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 TLR1/2 was up-regulated but TLR3 was down-regulated; immune regulation (PIgR, MHC2), apoptosis (Cytc, Casp3, BIRC5), stress response (HSP60/70/90, GRP94, Bip, HURP1) and iron homeostasis (Mfn1, TFR1, Hepc) related genes were up-regulated; complement (C1QL3, C1QBP, C7), chemokines and their receptors (LECT2, CXCR3/1/4, CCR2) related genes showed disordered expression. Several bacterial genera groups, such as Collinsella, Romboutsia, Phyllobacterium, Prevotella 9, and Prevotellaceae NK3B31, 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.
{"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}
Pub Date : 2025-09-20DOI: 10.1016/j.cbpc.2025.110360
Weiwei Xie , Qiaoqiao Zhang , Li Jin
Quantum dots (QDs) influence otolith development and locomotor behavior, although the underlying mechanism remain unclear. This study evaluated the toxicity of CdSe/ZnS QDs on otolith development and locomotor behavior in the next generation (F1) using rare minnows (Gobiocypris rarus) as model organisms. The sexually mature parents of rare minnows (F0) were exposed to varying concentrations of CdSe/ZnS QDs (0, 100, 200, 400 and 800 nmol/L) for four days, after which embryos were collected through artificial insemination. The results indicated that exposure to varying concentrations of QDs inhibited the growth of utricular and saccular otoliths in F1 larvae, evidenced by a decrease in otolith lateral area. Furthermore, an increase in malformations and mortality rate were observed, alongside reductions in swimming speed, movement distance and overall calcium content, ultimately resulting in loss of balance control in F1 larvae. Exposure to CdSe/ZnS QDs also suppressed the transcript expression of the atp2b1a, stm and sparc genes, while promoting the transcription of cahz, ecac and omp1 genes. Notably, the adverse effects of CdSe/ZnS QDs on otolith growth and swimming behavior could be mitigated by supplementing Ca2+ in the environment. Following calcium supplementation, the damage to otolith development in larvae was alleviated to some extent, and locomotor behavior returned to normal. Overall, the results suggest that CdSe/ZnS QDs can adversely affect otolith development and locomotor behavior in F1 larvae of rare minnows at both individual and molecular levels, ultimately leading to impaired swimming abilities and balance control.
{"title":"Parental exposure to CdSe/ZnS QDs affects otolith development and locomotor behavior in rare minnow (Gobiocypris rarus) offspring","authors":"Weiwei Xie , Qiaoqiao Zhang , Li Jin","doi":"10.1016/j.cbpc.2025.110360","DOIUrl":"10.1016/j.cbpc.2025.110360","url":null,"abstract":"<div><div>Quantum dots (QDs) influence otolith development and locomotor behavior, although the underlying mechanism remain unclear. This study evaluated the toxicity of CdSe/ZnS QDs on otolith development and locomotor behavior in the next generation (F1) using rare minnows (<em>Gobiocypris rarus</em>) as model organisms. The sexually mature parents of rare minnows (F0) were exposed to varying concentrations of CdSe/ZnS QDs (0, 100, 200, 400 and 800 nmol/L) for four days, after which embryos were collected through artificial insemination. The results indicated that exposure to varying concentrations of QDs inhibited the growth of utricular and saccular otoliths in F1 larvae, evidenced by a decrease in otolith lateral area. Furthermore, an increase in malformations and mortality rate were observed, alongside reductions in swimming speed, movement distance and overall calcium content, ultimately resulting in loss of balance control in F1 larvae. Exposure to CdSe/ZnS QDs also suppressed the transcript expression of the <em>atp2b1a</em>, <em>stm</em> and <em>sparc</em> genes, while promoting the transcription of <em>cahz</em>, <em>ecac</em> and <em>omp1</em> genes. Notably, the adverse effects of CdSe/ZnS QDs on otolith growth and swimming behavior could be mitigated by supplementing Ca<sup>2+</sup> in the environment. Following calcium supplementation, the damage to otolith development in larvae was alleviated to some extent, and locomotor behavior returned to normal. Overall, the results suggest that CdSe/ZnS QDs can adversely affect otolith development and locomotor behavior in F1 larvae of rare minnows at both individual and molecular levels, ultimately leading to impaired swimming abilities and balance control.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"299 ","pages":"Article 110360"},"PeriodicalIF":4.3,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-19DOI: 10.1016/j.cbpc.2025.110358
Qian Li , Wenjing Cheng , Hongyu Wang , Jun Chen , Yueyun Qin , Ruozhu Sheng , Shaohong Peng , Zaitian Li , Tao Lu , Liwei Sun
The hazardous effects of microplastics on aquatic biota have been extensively documented. However, the impact of surface functionalization on the toxicological profiles of microplastics, particularly in fish, requires further investigation. In the present study, the effects of polystyrene microplastics (50–100 nm in diameter), either non-functionalized or functionalized with carboxyl (-COOH) or amino (−NH2) groups, on zebrafish were explored. Exposure to all three types of microplastics (0.1, 1, and 10 mg/L) resulted in developmental toxicity in zebrafish at early life stages. This included increased mortality, reduced larval body length, decreased heart rate, impaired swimming ability, as well as disruptions in redox homeostasis, nervous system development, and immune responses. Moreover, all types of microplastics (1 mg/L) inhibited the regenerative capacity of larval zebrafish after caudal fin amputation, both morphologically and functionally. This inhibition was likely due to alterations in immune response, excessive production of reactive oxygen species, and disruptions in the signaling networks that regulate fin regeneration. Among the tested microplastics, amino-modified particles generally exhibited greater developmental toxicity and stronger inhibitory effects on fin regeneration. Our findings confirm that the functionalization of microplastics plays a crucial role in their interactions with biological systems and highlight concerns regarding the potential effects of functionalization, whether intentional or resulting from natural weathering processes.
{"title":"Developmental toxicity of functionalized polystyrene microplastics and their inhibitory effects on fin regeneration in zebrafish","authors":"Qian Li , Wenjing Cheng , Hongyu Wang , Jun Chen , Yueyun Qin , Ruozhu Sheng , Shaohong Peng , Zaitian Li , Tao Lu , Liwei Sun","doi":"10.1016/j.cbpc.2025.110358","DOIUrl":"10.1016/j.cbpc.2025.110358","url":null,"abstract":"<div><div>The hazardous effects of microplastics on aquatic biota have been extensively documented. However, the impact of surface functionalization on the toxicological profiles of microplastics, particularly in fish, requires further investigation. In the present study, the effects of polystyrene microplastics (50–100 nm in diameter), either non-functionalized or functionalized with carboxyl (-COOH) or amino (−NH<sub>2</sub>) groups, on zebrafish were explored. Exposure to all three types of microplastics (0.1, 1, and 10 mg/L) resulted in developmental toxicity in zebrafish at early life stages. This included increased mortality, reduced larval body length, decreased heart rate, impaired swimming ability, as well as disruptions in redox homeostasis, nervous system development, and immune responses. Moreover, all types of microplastics (1 mg/L) inhibited the regenerative capacity of larval zebrafish after caudal fin amputation, both morphologically and functionally. This inhibition was likely due to alterations in immune response, excessive production of reactive oxygen species, and disruptions in the signaling networks that regulate fin regeneration. Among the tested microplastics, amino-modified particles generally exhibited greater developmental toxicity and stronger inhibitory effects on fin regeneration. Our findings confirm that the functionalization of microplastics plays a crucial role in their interactions with biological systems and highlight concerns regarding the potential effects of functionalization, whether intentional or resulting from natural weathering processes.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"299 ","pages":"Article 110358"},"PeriodicalIF":4.3,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-19DOI: 10.1016/j.cbpc.2025.110361
Chaoyi Xie , Hongce Song , Junjie Li , Shuai Xu , Liqun Ren , Chunnuan Zhao , Yuping Wu , Xiaotong Wang , Biao Wu , Shubao Zhang , Haiying Han , Tao Yu
Microplastic (MP) pollution challenges marine ecosystems, with gastropods like Haliotis discus hannai being potentially vulnerable. However, the reversibility of MP-induced physiological damage in gastropods remains poorly understood. This study investigated the effects of polystyrene microplastics (PS-MPs; 0, 100, and 1000 μg/L) on H. discus hannai in a 14-day exposure followed by a 7-day recovery experimental design. The analysis focused on antioxidant status, energy metabolism, and immune pathways. Results showed dose-dependent oxidative stress during PS-MPs exposure, indicated by significantly (P < 0.05) elevated antioxidant enzyme activities (Superoxide dismutase, Catalase and Glutathione peroxidase), which decreased but did not normalize during recovery. Exposure to a low concentration of PS-MPs (100 μg/L) resulted in metabolic adjustments consistent with homeostatic maintenance, whereas a high concentration (1000 μg/L) significantly increased lactate dehydrogenase and Na+/K+-ATPase activities, suggesting metabolic disruption. These energy metabolism alterations persisted, showing incomplete recovery. Immune pathway analysis revealed minimal changes at low PS-MPs concentrations but significant enrichment of pathways like IL-17 and Fc-Epsilon-RI signaling at high concentrations during exposure. Notably, sustained activation of immune pathways, including NOD-like receptor, Toll-like receptor, and IL-17 signaling (particularly in the high-concentration group), persisted during recovery, potentially indicating prolonged cellular stress or links to apoptosis. Furthermore, Integrated Biomarker Response (IBR) analysis confirmed that H. discus hannai remained severely impacted even after the recovery period. This study provides crucial evidence on the complex toxicodynamics of PS-MPs in H. discus hannai, highlighting incomplete physiological recovery and significant damage during the recovery period following exposure, especially at high concentrations.
{"title":"The plastic threat to marine gastropods: Oxidative stress, energy metabolism and impaired recovery in juvenile abalone (Haliotis discus hannai) exposed to polystyrene microplastics","authors":"Chaoyi Xie , Hongce Song , Junjie Li , Shuai Xu , Liqun Ren , Chunnuan Zhao , Yuping Wu , Xiaotong Wang , Biao Wu , Shubao Zhang , Haiying Han , Tao Yu","doi":"10.1016/j.cbpc.2025.110361","DOIUrl":"10.1016/j.cbpc.2025.110361","url":null,"abstract":"<div><div>Microplastic (MP) pollution challenges marine ecosystems, with gastropods like <em>Haliotis discus hannai</em> being potentially vulnerable. However, the reversibility of MP-induced physiological damage in gastropods remains poorly understood. This study investigated the effects of polystyrene microplastics (PS-MPs; 0, 100, and 1000 μg/L) on <em>H. discus hannai</em> in a 14-day exposure followed by a 7-day recovery experimental design. The analysis focused on antioxidant status, energy metabolism, and immune pathways. Results showed dose-dependent oxidative stress during PS-MPs exposure, indicated by significantly (<em>P</em> < 0.05) elevated antioxidant enzyme activities (Superoxide dismutase, Catalase and Glutathione peroxidase), which decreased but did not normalize during recovery. Exposure to a low concentration of PS-MPs (100 μg/L) resulted in metabolic adjustments consistent with homeostatic maintenance, whereas a high concentration (1000 μg/L) significantly increased lactate dehydrogenase and Na<sup>+</sup>/K<sup>+</sup>-ATPase activities, suggesting metabolic disruption. These energy metabolism alterations persisted, showing incomplete recovery. Immune pathway analysis revealed minimal changes at low PS-MPs concentrations but significant enrichment of pathways like IL-17 and Fc-Epsilon-RI signaling at high concentrations during exposure. Notably, sustained activation of immune pathways, including NOD-like receptor, Toll-like receptor, and IL-17 signaling (particularly in the high-concentration group), persisted during recovery, potentially indicating prolonged cellular stress or links to apoptosis. Furthermore, Integrated Biomarker Response (IBR) analysis confirmed that <em>H. discus hannai</em> remained severely impacted even after the recovery period. This study provides crucial evidence on the complex toxicodynamics of PS-MPs in <em>H. discus hannai</em>, highlighting incomplete physiological recovery and significant damage during the recovery period following exposure, especially at high concentrations.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"299 ","pages":"Article 110361"},"PeriodicalIF":4.3,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145106964","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}