Comparative Biochemistry and Physiology C-toxicology & Pharmacology最新文献

{"title":"Disruption of mitochondrial homeostasis and apoptosis by oryzalin exposure in zebrafish embryos","authors":"Hahyun Park ,&nbsp;Taeyeon Hong ,&nbsp;Gwonhwa Song ,&nbsp;Whasun Lim","doi":"10.1016/j.cbpc.2025.110284","DOIUrl":"10.1016/j.cbpc.2025.110284","url":null,"abstract":"<div><div>Dinitroaniline compounds are important industrial chemicals widely used in dye manufacturing and pre-emergence pesticide production. They disrupt microtubule formation, leading to a higher proportion of cells arrested at metaphase during development. The potential toxicity of oryzalin, a dinitroaniline compound and a commonly used herbicide, toward nontarget organisms remains poorly understood. This study evaluated the developmental toxicity of oryzalin using zebrafish embryos as an in vivo model, given their rapid organogenesis and sensitivity to chemical exposure during early development. To investigate the toxic effects of oryzalin, we conducted developmental toxicity assessments using zebrafish embryos. Interestingly, low-dose exposure to oryzalin caused severe developmental abnormalities, significantly impairing the survival and growth of the embryos. Fluorescent imaging of multiple transgenic zebrafish lines (<em>fli1a</em>;<em>eGFP</em> and <em>l-fabp</em>;<em>dsRed</em>) revealed that oryzalin exposure disrupted liver organogenesis and vascular network formation. Furthermore, transcriptional alterations in essential genes associated with early developmental stages further supported the observed abnormalities. Mitochondrial dysfunction triggered by oryzalin was found to promote oxidative stress and apoptosis. These findings suggest that dinitroaniline compounds, such as oryzalin, may pose developmental toxicity risks to vertebrates, highlighting the need for caution in their extensive use.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"297 ","pages":"Article 110284"},"PeriodicalIF":3.9,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596022","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":"Renal protective efficiency of Isatin-linked Pyrazole (3E) derivative which mitigates gentamicin-induced nephrotoxicity and its anti-fibrotic mechanisms in an in-vivo zebrafish model","authors":"S. Madesh ,&nbsp;Karthikeyan Ramamurthy ,&nbsp;Sanjay Gopi ,&nbsp;Marapatla Shiny ,&nbsp;Girija Sastry Vedula ,&nbsp;Ilavenil Soundharrajan ,&nbsp;Bader O. Almutairi ,&nbsp;Kathiravan Muthu Kumaradoss ,&nbsp;S. Karthick Raja Namasivayam ,&nbsp;Jesu Arockiaraj","doi":"10.1016/j.cbpc.2025.110274","DOIUrl":"10.1016/j.cbpc.2025.110274","url":null,"abstract":"<div><div>Gentamicin (Gen), a commonly used aminoglycoside antibiotic, is associated with significant nephrotoxicity driven by oxidative stress, inflammation, and fibrosis, leading to renal impairment. This study investigates the therapeutic potential of the Isatin-linked Pyrazole (3E) derivative (or compound) in mitigating Gen-induced nephrotoxicity using <em>in-vivo</em> zebrafish as a model organism. The anti-inflammatory, antioxidant, and anti-fibrotic properties of the 3E derivative were assessed through biochemical, molecular, and histopathological analyses. The 3E compound demonstrated concentration-dependent anti-inflammatory activity, significantly reducing nitric oxide production, proteinase activity, and hemolysis and maintaining the safest dosages in zebrafish embryos. Treatment with 3E effectively restored antioxidant enzyme levels (SOD, CAT, and GST) and reduced oxidative damage markers, including LDH, compared to the Gen-treated group. Additionally, 3E ameliorated Gen-induced glomerular filtration damage and collagen deposition in kidney tissues, as evidenced by reduced hydroxyproline levels and creatinine and urea excretion rate. Molecular analyses revealed that 3E significantly downregulated pro-inflammatory (<em>il-1β</em>, <em>tnfα</em>) and pro-fibrotic (<em>tgf-β1a</em>, <em>mmp9</em>) genes, correlating with histological improvements in glomerular and tubular architecture. Furthermore, the model limitations in translating results to human physiology, the findings highlight 3E's therapeutic potential for nephroprotection by targeting key mechanisms underlying renal injury. Future studies are warranted to elucidate the molecular pathways and validate the efficacy of 3E in mammalian models.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"297 ","pages":"Article 110274"},"PeriodicalIF":3.9,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596015","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":"Exacerbating cadmium toxicity disrupts metabolism in black sea bass under marine heatwaves: insights from physiological and metabolic responses","authors":"Qing Ji ,&nbsp;Jie Lian ,&nbsp;Jiachen Yu ,&nbsp;Xingqiang Wang ,&nbsp;Mei Cao ,&nbsp;Bo Yang","doi":"10.1016/j.cbpc.2025.110279","DOIUrl":"10.1016/j.cbpc.2025.110279","url":null,"abstract":"<div><div>Marine heatwaves (MHWs) and cadmium (Cd²⁺) pollution are escalating threats to marine ecosystems, yet their combined effects on marine fish remain poorly understood. This study investigates the metabolic responses of juvenile black sea bass (<em>Centropristis striata</em>) to Cd²⁺ exposure and MHWs-induced heat stress, focusing on carbohydrate and lipid metabolism in the liver. Fish were exposed to Cd²⁺ (0, 1.83, and 6.4 mg/L) at 17 °C and 30 °C for 96 h. The results demonstrate that elevated temperature markedly increases Cd²⁺ bioaccumulation, with hepatic tissues showing the highest accumulation. Under combined Cd²⁺ and heat stress, glycolysis is initially activated (increased <em>pk</em> levels and LDH activity) but inhibited after 96 h (decreased <em>pfk</em> levels). Concurrently, upregulation of <em>pepck</em> and increased Glu levels indicate compensatory gluconeogenesis. Additionally, rising Cd²⁺ concentrations elevate liver TG, TC, and mRNA levels of <em>fasn</em>, <em>scd</em>, <em>cpt1</em>, and <em>ppar-γ</em>, while suppressing <em>ppar-α</em>. Co-exposure groups showed more pronounced changes than single-exposure groups. These findings suggest that black sea bass liver enhances fatty acid oxidation for energy and promotes lipid storage under stress. Oil Red O staining revealed significantly enlarged lipid droplets in the liver of the co-exposure group, confirming that heat stress exacerbates Cd²⁺-induced lipid accumulation. Prolonged exposure leads to energy depletion and oxidative stress. This study highlights the synergistic toxicity of Cd²⁺ and MHWs, underscoring the need for strategies to mitigate climate change and heavy metal impacts on marine ecosystems.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"297 ","pages":"Article 110279"},"PeriodicalIF":3.9,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144570821","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":"Influence of prolonged exposure to acetamiprid on the toxicology of the decapod crustacean Pacific white shrimp Penaeus vannamei","authors":"Zhen-Fei Li ,&nbsp;Zhi Luo ,&nbsp;Zhi-Yu Lin ,&nbsp;Zhen-Qiang Fu ,&nbsp;Feng-Lu Han ,&nbsp;Er-Chao Li","doi":"10.1016/j.cbpc.2025.110277","DOIUrl":"10.1016/j.cbpc.2025.110277","url":null,"abstract":"<div><div>Neonicotinoid insecticides have raised increasing concerns due to their toxic effects on aquatic invertebrates, potentially contributing to population declines and aquatic food web disruption. This study investigated the chronic toxicity of the first-generation neonicotinoid acetamiprid on <em>Penaeus vannamei</em> using physiological, biochemical, and transcriptomic approaches. After 28 days of exposure, significant reductions in survival rate, growth performance, and hepatosomatic index were observed, with a calculated 96 h LC₅₀ of 60.81 μg/L. Acetamiprid exposure led to oxidative stress, as indicated by altered antioxidant enzyme activities and the downregulation of related genes. Genes involved in circadian rhythm, thyroid hormone, and neurotrophin signaling pathways were significantly suppressed. Additionally, Phase I detoxification genes (e.g., CYP450 family) were upregulated, while Phase II genes (e.g., GSTs) were downregulated, suggesting a disrupted detoxification mechanism. These findings suggest that <em>P. vannamei</em> is sensitive to acetamiprid, and prolonged exposure may impair growth and physiological homeostasis through oxidative and neuroendocrine disturbances. This study provides insights into the potential ecological risks of acetamiprid in aquaculture environments.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"297 ","pages":"Article 110277"},"PeriodicalIF":3.9,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144570822","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":"Combined exposure to fenvalerate and tebuconazole induces apoptosis, leading to developmental and endocrine toxicity in early life stages of Japanese Medaka (Oryzias latipes)","authors":"Muhammad Jawad ,&nbsp;Haijing Xu ,&nbsp;Sana Nasir ,&nbsp;Mengzhou Wu ,&nbsp;Junqiang Qiu ,&nbsp;Mingyou Li","doi":"10.1016/j.cbpc.2025.110280","DOIUrl":"10.1016/j.cbpc.2025.110280","url":null,"abstract":"<div><div>Pesticide residues in aquatic ecosystems often occur as complex mixtures, posing significant risks to aquatic fauna. However, the toxicological effects of fenvalerate (FEN) and tebuconazole (TEB) on marine and freshwater aquatic organisms are poorly studied. To evaluate the impact of fenvalerate and tebuconazole on the early development of Japanese medaka (<em>Oryzias latipes</em>), embryos and larvae were exposed to FEN (3 × 10⁻³ mg/L), TEB (1 mg/L), and a combined treatment of FEN+TEB (1 × 10⁻³ mg/L + 0.1 mg/L). The results showed that the combined exposure significantly reduced hatchability, survival rate, and heartbeat rate, indicating a synergistic effect. Morphological abnormalities were observed in embryos and newly hatched larvae, such as pericardial edema, yolk sac extension, curved spine, and caudal fin abnormalities. Apoptosis was induced in both single and combined mixture toxicity, as evidenced by upregulated expression of pro-apoptotic genes (<em>bax</em>, <em>p53</em>, and <em>caspase3</em>). Furthermore, key genes in the hypothalamic-pituitary-gonadal (HPG) axis (<em>cyp19a</em>, <em>cyp17</em>, <em>fshr</em>, <em>lhr</em>, <em>erα</em>, <em>erβ</em>) and reproduction-related genes (<em>vtg1</em> and <em>vtg2</em>) were downregulated, while <em>star</em> was upregulated in the binary mixture group. These results suggest that combined exposure to FEN and TEB induces synergistic toxicity, leading to increased mortality, developmental abnormalities, and endocrine disruption. This study enhances understanding of the molecular mechanisms underlying embryonic and larval development and underscores the importance of assessing the risk of pesticide mixtures in aquatic ecosystems.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"297 ","pages":"Article 110280"},"PeriodicalIF":3.9,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144587467","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":"Glyceraldehyde and glyceraldehyde-derived advanced glycation end-products have negative effect on chicken myoblasts","authors":"Meiko Okino ,&nbsp;Chikato Yamashita ,&nbsp;Masayoshi Takeuchi ,&nbsp;Ryosuke Makino ,&nbsp;Tetsuya Tachibana","doi":"10.1016/j.cbpc.2025.110283","DOIUrl":"10.1016/j.cbpc.2025.110283","url":null,"abstract":"<div><div>Advanced glycation end-products (AGEs) are formed through glycation between reducing sugars or their metabolites, including glyceraldehyde (GA). AGEs are associated with various chronic diseases in humans. Among them, GA-derived AGEs (GA-AGEs) exhibit strong toxicity in several cell types and are considered toxic AGEs. However, the effects of GA and GA-AGEs have not been examined in birds. The present study investigated whether GA and GA-AGEs negatively affect chicken embryo myoblasts. Myoblasts exposed to GA became sparse and small and exhibited a significant reduction in intracellular nicotinamide adenine dinucleotide (NADH) levels. Since the GA-induced decrease in NADH level was attenuated by aminoguanidine, which inhibits glycation and the production of AGEs, the effect would be attributed to the GA-AGEs, at least in part. Indeed, GA-AGEs itself also significantly decreased the intracellular NADH level. On the other hand, GA and GA-AGEs did not induce cell death such as apoptosis, and the production of reactive oxygen species in chicken myoblasts. Furthermore, neither GA nor GA-AGEs reduced the ratio of ATP levels to the total amount of ATP and ADP. In addition, GA did not affect mitochondrial membrane potential, whereas GA-AGEs decreased it. These results demonstrated that GA- and GA-AGEs decreased the intracellular NADH levels in chicken myoblasts, and the effect would not be due to cell death but the decrease in cell number.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"297 ","pages":"Article 110283"},"PeriodicalIF":3.9,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590627","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":"Enhancement of 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity by lipopolysaccharide in developing zebrafish lacking canonical pattern recognition pathways","authors":"Hayato Kitamura ,&nbsp;Katsuki Tanaka ,&nbsp;Huan Wang ,&nbsp;Tatsuro Nakamura ,&nbsp;Makoto Kobayashi ,&nbsp;Hiroki Teraoka","doi":"10.1016/j.cbpc.2025.110261","DOIUrl":"10.1016/j.cbpc.2025.110261","url":null,"abstract":"<div><div>Lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, is known to be a major inducer of inflammatory responses through Toll-like receptor 4 (TLR4) in mammals. The potentiation of aryl hydrocarbon receptor (AHR)-mediated responses by LPS has been reported in mammalian systems. However, in contrast to mammals, the zebrafish TLR4 homolog does not recognize LPS. This study investigated the effects of LPS on 2,3,7,8-tetrachlorodibenzo-<em>p</em>-dioxin (TCDD)-induced pre-cardiac edema in zebrafish larvae. Waterborne LPS alone had no effect on edema; however, it induced edema in the presence of 0.1 ppb TCDD, a concentration ineffective in inducing edema alone. LPS did not affect the expression of type 2 AHR (AHR2) and cytochrome P450 1 A, regardless of the presence of TCDD. Edema induced by LPS and TCDD was reduced by a thromboxane receptor (TP) antagonist, a prostacyclin receptor agonist, an antioxidant, and an activator of nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of antioxidant responses. Furthermore, LPS enhanced TP-induced edema in a manner sensitive to antioxidants and Nrf2 inducers. These results suggest that LPS enhances TP receptor signaling through oxidative stress, leading to increased edema in developing zebrafish exposed to TCDD.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"297 ","pages":"Article 110261"},"PeriodicalIF":3.9,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144570823","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":"Antioxidant effect of esculin and sulforaphane in zebrafish larvae: A comparative study","authors":"Srija Babu,&nbsp;Vignesh Sundarraja,&nbsp;Suryaa Manoharan,&nbsp;Ekambaram Perumal","doi":"10.1016/j.cbpc.2025.110264","DOIUrl":"10.1016/j.cbpc.2025.110264","url":null,"abstract":"<div><div>Antioxidants are crucial for maintaining cellular redox homeostasis by neutralizing free radicals, including reactive oxygen species (ROS). Nuclear factor erythroid-2-related factor 2 (Nrf2) is a transcription factor that activates various cytoprotective genes to counteract oxidative damage. The present study aimed to compare the antioxidant potential of natural phytochemicals, esculin (ESC), and sulforaphane (SFN) in zebrafish larvae, focusing on Nrf2 activation. Zebrafish larvae were treated with ESC (100 μM) and SFN (40 μM) along with control for 6 h. The levels of ROS, lipid peroxidation (LPO), nitric oxide (NO), glutathione S-transferase (GST), glutathione peroxidase (GPx), catalase (CAT), and reduced glutathione (GSH) were measured. Further, RT-PCR and Western blotting methods were employed to determine the antioxidant genes and protein levels, respectively. In addition, Nrf2 localization within the cell was assessed using nuclear/cytosolic fractionation assay and wholemount immunohistochemistry method. Our results demonstrate that ESC treatment significantly increased antioxidant enzyme activities (GST, GPx, CAT), similar to the effects observed with SFN. Further, ESC enhanced the mRNA levels of antioxidant genes expression, such as <em>nrf2, gstp1, hmox1a, prdx1, nqo1, gss, gsr, sqstm1, hsp90aa1.2</em> than SFN. Antioxidant proteins Nrf2, Gstp1, Cat, and Sod2 were upregulated in the ESC-treated groups. Subsequently, nuclear localization of Nrf2 was detected in both SFN- and ESC-treated groups, confirming Nrf2 translocation into the nucleus. Our findings suggest that ESC possesses potent antioxidant activity as SFN in 72-hpf zebrafish larvae through the Keap1-Nrf2 signaling pathway.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"297 ","pages":"Article 110264"},"PeriodicalIF":3.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567248","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":"Integrated analysis of lncRNA-miRNA-mRNA regulatory network revealing molecular mechanisms of immune response and ion transport in Eriocheir sinensis under alkalinity stress","authors":"Jun-Lei Ma ,&nbsp;Yu-Lin Bai ,&nbsp;Yi-Dong Liang ,&nbsp;Ting Zhang ,&nbsp;Lei You ,&nbsp;Dong-Po Xu","doi":"10.1016/j.cbpc.2025.110262","DOIUrl":"10.1016/j.cbpc.2025.110262","url":null,"abstract":"<div><div>High alkalinity stress threatens to aquatic animal survival. However, research on the alkalinity tolerance and adaptation mechanisms of crustaceans remains limited. This study assessed the Chinese mitten crab's (<em>Eriocheir sinensis</em>) tolerance to alkalinity and investigated its adaptation mechanism through physiological, histological, and whole transcriptome analysis of gills. Acute alkalinity stress experiments showed that the alkalinity 96 h-LC50 for <em>E. sinensis</em> was 66.97 mmol/L. The experiment constructed a high alkalinity group (33.5 mmol/L, NHC) and a control group (0 mmol/L, CL) model. The gill filaments in the NHC group exhibited structural damage, including curling, atrophy, and cell vacuolation, along with the manifestation of oxidative stress. Between the NHC group and CL group, a total of 1047 differentially expressed (DE) lncRNAs, 70 DE miRNAs, and 1191 DE mRNAs were obtained. KEGG and GO enrichment analysis found that they were mainly enriched in immune and metabolic pathways, such as the mTOR signaling pathway, TGF-beta signaling pathway, NOD-like receptor signaling pathway, carbohydrate metabolism, and amino acid metabolism pathway. Through the analysis of targeting relationships and screening of target genes related to immune responses, ion transport, and apoptosis, a total of 11 lncRNAs, 6 miRNAs, and 8 mRNAs were obtained for constructing the lncRNA-miRNA-mRNA regulatory network. The findings of this study demonstrate that under high alkaline stress conditions, both the innate immune response and ion transport are enhanced in the gills. This research elucidates the molecular mechanisms underlying gill-mediated high environmental alkalinity stress in crustaceans, which also offers a theoretical foundation for <em>E. sinensis</em> saline-alkaline aquaculture.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"297 ","pages":"Article 110262"},"PeriodicalIF":3.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552522","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":"Maternal exposure to norfloxacin induces impairment of cardiac development in zebrafish offspring","authors":"Chongqian Bian,&nbsp;Zhaobo Xun,&nbsp;Yiyang Fu,&nbsp;Zilong Wang,&nbsp;Jijia Wang,&nbsp;Lang Wu","doi":"10.1016/j.cbpc.2025.110263","DOIUrl":"10.1016/j.cbpc.2025.110263","url":null,"abstract":"<div><div>Fluoroquinolone antibiotics (FQs) play a crucial role in human and animal medicine, but their increasing use and high persistence have posed serious threats to ecosystems and public health. FQs have been found to be associated with heart developmental defects. However, the intergenerational effects of FQs on fish cardiac development remain poorly understood. Here we investigated the chronic effects of maternal exposure to environmentally related concentrations of norfloxacin (NOR) on cardiac development in zebrafish offspring. Our results showed that maternal NOR exposure resulted in increased mortality and malformation rates, impaired cardiac function and changes in cardiac phenotype, including larger cardiac looping angles, longer ventricular and increased distance between sinus venosus and bulbus arteriosus (SV-BA distance) in zebrafish offspring. Expression of genes involved in early cardiac development (<em>myl7</em>, <em>vmhc</em>, <em>gata4</em>, <em>tbx1</em>, <em>tbx5</em>, and <em>nkx2.5</em>) showed disorder. Maternal NOR exposure impairs cardiac looping by altering transcription levels of non-canonical WNT/PCP pathway genes (<em>wnt11</em>, <em>fzd7a</em>, and <em>vangl2</em>). Additionally, offspring of zebrafish following maternal NOR exposure showed increase in oxidative stress and apoptotic level. Meanwhile, genes associated with histone methylation (<em>kdm6a</em>, <em>kdm6b</em>, <em>hoxd11a</em>, <em>hoxd9</em>, and <em>hoxd10</em>) were up-regulated. Taken together, our results suggest that maternal NOR exposure cause cardiotoxicity in zebrafish offspring, possibly through inducing oxidative stress, promoting apoptosis, and regulating genes expression involved in cardiac development. We speculate that the intergenerational mechanisms of NOR action are likely to be related with histone modifications. Our study provides new insights into the potential risks and mechanisms underlying cardiotoxicity in fish offspring following maternal exposure to NOR.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"297 ","pages":"Article 110263"},"PeriodicalIF":3.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552523","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}