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

{"title":"Developmental and neurobehavioral toxicity of di-(2-ethylhexyl) phthalate (DEHP) in zebrafish larvae","authors":"Garima Jindal ,&nbsp;Anuradha Mangla ,&nbsp;Poonam Goswami ,&nbsp;Mehjbeen Javed ,&nbsp;Mohd. Anas Saifi ,&nbsp;Iqra Mazahir ,&nbsp;Padmshree Mudgal ,&nbsp;Basir Ahmad ,&nbsp;Sheikh Raisuddin","doi":"10.1016/j.cbpc.2025.110254","DOIUrl":"10.1016/j.cbpc.2025.110254","url":null,"abstract":"<div><div>Di-ethyl hexyl phthalate (DEHP), a plasticizer used in medical devices and cosmetics, easily leaches into the environment due to its weak chemical bonds with plastics. Humans and other organisms are exposed to DEHP through inhalation, ingestion, and dermal contact, inflicting toxic effects like neurotoxicity, hepatotoxicity, and reproductive toxicity. However, there is a lack of information on its developmental toxicity, and its role in demyelination is also not well understood. We explored the adverse effects of DEHP during the early developmental stage of zebrafish larvae, focusing on its deteriorative impact on the nervous system through demyelination at various concentrations (10, 20, 50, 100, and 200 ppm). Cuprizone was used as a positive control compound. Various markers of oxidative stress, hormonal changes, and altered expression of myelin-related protein were measured in larvae exposed to DEHP. Results showed that higher concentrations of DEHP had lethal effects on zebrafish larvae. The activity of acetylcholinesterase (AChE) and the level of reduced glutathione (GSH) were significantly decreased, while lipid peroxidation (LPO) and glutathione <em>S-</em>transferase (GST) activity were significantly increased. Additionally, cortisol and thyroxine levels were notably decreased, together with decreased mRNA expression of the myelin sheath and its cell markers such as myelin basic protein (<em>mbp</em>), SRY-box transcription factor (<em>sox10</em>), and oligodendrocyte lineage transcription factor 2 (<em>o</em><em>lig2</em>) in the DEHP-treated larvae. Similarly, protein expression of Mbp, Sox10, and Olig2 was also reduced. Overall, this study offers an understanding of the developmental neurotoxicity of DEHP and its behavioral and demyelinating effects in zebrafish larvae during early developmental stages.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"296 ","pages":"Article 110254"},"PeriodicalIF":3.9,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309668","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":"Roundup Transorb reduces growth and expression of somatotropic axis genes in the silverside Odontesthes argentinesis fish larvae","authors":"Maidana Idiarte ,&nbsp;Vinicius Farias Campos ,&nbsp;Amanda Weege da Silveira Martins ,&nbsp;Nivia Maria Streit ,&nbsp;Gilson de Mendonça ,&nbsp;Ricardo Berteaux Robaldo","doi":"10.1016/j.cbpc.2025.110256","DOIUrl":"10.1016/j.cbpc.2025.110256","url":null,"abstract":"<div><div>Despite the use of herbicides has led to substantial increases in agricultural production, it has also introduced a series of environmental challenges that pose threats to the survival of non-target species in both terrestrial and aquatic ecosystems. Species of the genus <em>Odontesthes</em> have significant economic importance as they are valuable resources for artisanal fishing and local populations' income. Moreover, these organisms serve as crucial biological models in ecotoxicological and genetic research. Given the ecological and economic importance of <em>Odontesthes argentinensis</em>, this research aimed to investigate how the gene expression of the somatotropic axis (<em>gh, ghr1, ghr2, igf1,</em> and <em>igf2</em>) is impacted by the herbicide Roundup Transorb (RT), validating them as reliable biomarkers of exposure. <em>O. argentinensis</em> larvae were exposed to glyphosate at concentrations of 0.36, 1.8, and 3.6 mg/L for 96 h. The results indicate that there was a reduction in the expression of all analyzed genes in animals exposed to RT, resulting in decreased body growth. The expression of genes in the somatotropic axis was thus established as an effective biomarker for assessing exposure to Roundup Transorb herbicide.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"296 ","pages":"Article 110256"},"PeriodicalIF":3.9,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144307935","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":"Protective effects of metformin against volatile organic compounds-induced developmental toxicity in zebrafish embryos","authors":"Jieru Lu ,&nbsp;Zhuoyan Li ,&nbsp;Xuehua Ruan ,&nbsp;Lihui Jin ,&nbsp;Xiaogang Yu ,&nbsp;Xin Zhou ,&nbsp;Jianyuan Zhao ,&nbsp;Yurong Wu ,&nbsp;Sun Chen ,&nbsp;Kun Sun ,&nbsp;Jing Sun","doi":"10.1016/j.cbpc.2025.110250","DOIUrl":"10.1016/j.cbpc.2025.110250","url":null,"abstract":"<div><div>Volatile organic compounds (VOCs) are widespread environmental pollutants associated with various health risks, including developmental toxicity. Our previous studies revealed a correlation between indoor VOCs exposure and an increased risk of congenital heart diseases (CHDs), which was confirmed by establishing a zebrafish exposure model. Metformin (MET), a classic hypoglycemic drug, has been identified to possess multiple properties. Based on previous research on the protective effects of metformin on air pollution, we propose a hypothesis of using metformin as protective agent against VOCs-induced developmental toxicity in zebrafish embryos and explore the underlying molecular mechanisms.</div><div>The zebrafish embryos were exposed to the VOCs mixture (128 mg/L) alone or in combination with different concentrations of MET (0.5, 1.0 and 2.0 mg/mL) for 120 h. Toxicological indicators such as survival rate, hatching rate and morphological abnormalities (spinal curvature, yolk sac edema and body length reduction) were significantly alleviated by MET, especially in concentrations of 0.5 mg/mL. MET treatment effectively mitigated both cardiovascular impairments (pericardial edema and bradycardia) and neurodevelopmental deficits (locomotor activity). Transcriptomic profiling revealed MET-mediated modulation of apoptosis-related genes and cell cycle regulators. Pathway analyses identified significant enrichment in neurodevelopmental and cardiovascular functions, corroborated by acridine orange staining showing reduced apoptosis.</div><div>Our findings demonstrate MET's anti-apoptotic protection against VOCs-induced developmental toxicity, suggesting its potential as a novel therapeutic intervention for pollution-related developmental disorders.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"296 ","pages":"Article 110250"},"PeriodicalIF":3.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144255311","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":"Physiological and histopathological response of non-target organisms to emamectin benzoate: an effective innovative insecticide or a new ecosystem health hazard?","authors":"Meryem Bayrak ,&nbsp;Pınar Arslan Yüce ,&nbsp;Aysel Çağlan Günal ,&nbsp;Göktuğ Gül ,&nbsp;Cristiana Roberta Multisanti ,&nbsp;Caterina Faggio","doi":"10.1016/j.cbpc.2025.110241","DOIUrl":"10.1016/j.cbpc.2025.110241","url":null,"abstract":"<div><div>Emamectin benzoate (EB) is a macrocyclic lactone insecticide, belonging to the avermectins class and ivermectin family and is produced by <em>Streptomyces avermitilis</em>. EB is widely used in agriculture and aquaculture to reduce the damaging effects of pests. This study aimed to investigate the 1) acute toxicity (median lethal concentration values, LC₅₀) and 2) sublethal toxicity (immunological, biochemical and histopathological effects of sublethal concentrations) of EB on non-target freshwater mussels (<em>Unio delicatus</em>). The 96-h LC₅₀ value of EB for <em>U. delicatus</em> was determined as 0.21 mg/L. <em>U. delicatus</em> individuals were exposed to sublethal concentrations at ¹/₁₀ and ¹/₁₀₀ of the LC₅₀ value for 48 h, 7d and 21d. Acute exposure to sub-lethal concentrations resulted in a significant decrease in the total haemocyte count compared to the control groups (<em>p</em> &lt; 0.05). Changes in total antioxidant status and total oxidant levels occurred in the haemolymph. While changes in gill and digestive gland glutathione and advanced oxidation protein products were not significant during acute (48 h and 7d) and chronic (21d) exposure to sub-lethal concentrations of EB, significant increases or decreases were observed in malondialdehyde, compared to control groups (<em>p</em> &lt; 0.05). In addition to immunological and biochemical changes, histopathological changes were observed in gill and digestive gland tissues. The results of this study showed that exposure to EB at two sublethal concentrations in <em>U. delicatus</em> caused biochemical and histopathological changes in the tissues of the haemolymph, gills and digestive glands. The overall results of this study showed that EB is toxic to mussels even at sub-lethal concentrations in acute and chronic exposure.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"296 ","pages":"Article 110241"},"PeriodicalIF":3.9,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184574","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":"Chronic toxicity of antibiotics and global warming in Danio rerio: Biomarker responses and toxicological effects","authors":"Bárbara S. Diogo ,&nbsp;Sara Rodrigues ,&nbsp;Bent Speksnijder ,&nbsp;Oksana Golovko ,&nbsp;Sara C. Antunes","doi":"10.1016/j.cbpc.2025.110240","DOIUrl":"10.1016/j.cbpc.2025.110240","url":null,"abstract":"<div><div>The combined influence of multiple stress factors on natural ecosystems is a critical concern, as neglecting their effects could compromise essential biological functions. However, limited studies have explored the combined effects of antibiotics and global warming on aquatic ecosystems, leaving a gap in understanding their interaction. This study aimed to assess the toxicity of environmentally relevant concentrations of sulfamethoxazole (SMX: 150 μg/L), trimethoprim (TRIM: 30 μg/L), and their mixture (MIX: 150 μg SMX/L + 30 μg TRIM/L) on <em>Danio rerio</em> at three temperature conditions: standard (26 °C), moderately high (28 °C), and high (32 °C) temperatures. A multi-biomarker approach was used to evaluate the organism's biological status (e.g., antioxidant/detoxification defense enzymes, lipid peroxidation, cholinergic neurotransmission, energetic metabolism, DNA damage). Results indicated that rising temperatures influenced the toxicity level of each antibiotic differently to <em>D. rerio</em>. At 26 °C, all the antibiotics were marginally toxic, and major alterations were observed (oxidative stress and neurotoxicity). Increasing temperature to 28 °C, the toxicity increased, with SMX and MIX exhibiting moderate toxicity, and severe alterations (neurotoxicity and DNA damage). In contrast, TRIM showed only slight toxicity and recorded negligible alterations (antioxidant defense alterations). At higher temperature (32 °C) individual antibiotics revealed slightly toxic with negligible alterations. However, MIX at 32 °C was more toxic, and severe damage was observed (e.g., higher DNA damage). These findings reveal a pressing and alarming threat: combined contaminants impact and climate change could drive aquatic ecosystems toward collapse. Understanding how these stressors interact is critical to preventing potentially irreversible damage to aquatic life.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"296 ","pages":"Article 110240"},"PeriodicalIF":3.9,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198450","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":"Ecotoxicological impacts of fipronil sulfone: Developmental and behavioral disruptions in zebrafish embryos and larvae","authors":"Bianca de Arruda Leite ,&nbsp;Bruno Rossato ,&nbsp;Carlos Gravato ,&nbsp;Daniel Junqueira Dorta ,&nbsp;Danielle Palma de Oliveira","doi":"10.1016/j.cbpc.2025.110236","DOIUrl":"10.1016/j.cbpc.2025.110236","url":null,"abstract":"<div><div>Fipronil sulfone is a persistent oxidative metabolite of the insecticide fipronil, frequently detected in aquatic systems and known to exert neurotoxic effects on non-target organisms. Despite its environmental relevance, the developmental impacts of fipronil sulfone remain underexplored. In this study, zebrafish embryos and larvae were exposed to environmentally relevant concentrations of fipronil sulfone (12.5–1000 μg/L) at different developmental stages (24, 48, 72, 120, and 144 hpf). Morphological, behavioral, and biochemical endpoints were assessed. Exposure to concentrations ≥125 μg/L significantly reduced swim bladder inflation (up to 100 % inhibition at ≥250 μg/L) and induced spinal curvature in over 60 % of larvae. Survival decreased progressively with increasing concentrations, reaching 100 % mortality at 1000 μg/L. Larvae exposed to 125 μg/L also exhibited hyperactivity followed by reduced locomotion, likely due to blocked GABAergic receptors and acetylcholinesterase inhibition. Moreover, oxidative stress was confirmed by increased reactive oxygen species and glutathione S-transferase activity. These findings demonstrate that even low concentrations of fipronil sulfone can compromise neurodevelopment and survival in zebrafish, underscoring the need for its inclusion in environmental monitoring and risk assessment frameworks.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"296 ","pages":"Article 110236"},"PeriodicalIF":3.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186743","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":"Lycopene alleviates splenic injury in grass carp (Ctenopharyngodon idella) caused by endoplasmic reticulum stress-autophagy axis induced by sulfamethoxazole through regulating AKT/AMPK pathway","authors":"Shuni Wang ,&nbsp;Yingxue Zhang ,&nbsp;Wangjuan Hu,&nbsp;Gaorong Zan,&nbsp;Yaxuan He,&nbsp;Mingwei Xing,&nbsp;Hongjing Zhao","doi":"10.1016/j.cbpc.2025.110239","DOIUrl":"10.1016/j.cbpc.2025.110239","url":null,"abstract":"<div><div>Sulfamethozole (SMZ), an antibiotic widely used in aquaculture, is bioaccumulating and resistant to degradation, posing ecological risks. Although environmentally relevant SMZ concentrations (0.3 μg/L) are known to impair piscine immune function, the molecular mechanisms driving its toxicity remain elusive. Lycopene (LYC) is a potent bioactive compound that alleviates SMZ-induced toxicity by regulating the endoplasmic reticulum (ER) stress autophagy axis. This experiment chooses 120 grass carps, divided into 4 groups: control group (CON), SMZ exposure group (0.3 μg/L), the LYC supplement group (10 mg/kg) and SMZ + LYC combined treatment group. The toxicity of SMZ (0.3 μg/L) to grass carp and the mitigation effect of LYC (10 mg/kg) to SMZ were studied through a 30-day experiment. Histopathological alterations were evaluated via hematoxylin-eosin (H&amp;E) staining, ultrastructural changes were visualized by transmission electron microscopy (TEM), and key biomarkers of ER stress, autophagy, and AKT/AMPK signaling were quantified through qRT-PCR and Western blotting. Results demonstrated that SMZ exposure induced disorganization of white pulp, cellular vacuolation, and activation of melanomacrophage centers (MMCs), accompanied by significant upregulation of ER stress markers (IRE1, PERK, ATF6, GRP78, eif2α) and autophagy-related genes (LC3, P62, Beclin1, ATG5). TEM revealed nuclear pyknosis, mitochondrial swelling, and increased autophagosomes in SMZ-treated splenocytes. LYC intervention markedly attenuated these pathological injuries and suppressed ER stress and excessive autophagy by modulating the AKT/AMPK pathway. Molecular docking analysis confirmed binding affinity between LYC and AKT/AMPK proteins, with a binding energy of −8.8 kcal/mol. Our findings establish a mechanistic foundation for developing LYC-enriched functional feeds to counteract antibiotic-associated ecological risks in sustainable aquaculture.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"296 ","pages":"Article 110239"},"PeriodicalIF":3.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168941","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":"Can Ahiflower® (Buglossoides arvensis) seed-oil supplementation help overcome the adverse effects of imidacloprid in honey bees?","authors":"Hichem A. Menail ,&nbsp;Samuel Robichaud ,&nbsp;Robert Cormier ,&nbsp;Arianne Blanchard ,&nbsp;Florence Hunter-Manseau ,&nbsp;Adèle Léger ,&nbsp;Simon G. Lamarre ,&nbsp;Nicolas Pichaud","doi":"10.1016/j.cbpc.2025.110238","DOIUrl":"10.1016/j.cbpc.2025.110238","url":null,"abstract":"<div><div>In this study, we investigated the effects of nutritional supplementation as a strategy to mitigate the impacts of imidacloprid (neonicotinoid) on honey bees by using Ahiflower® (<em>Buglossoides arvensis</em>) seed-oil. This oil is rich in stearidonic-acid (SDA, 18:4n3), which is a precursor to eicosapentaenoic-acid (EPA) and docosahexaenoic-acid (DHA) that are known for their beneficial and protective effects. Specifically, we chronically fed newly emerged worker bees with sucrose syrup and pollen patties (control) that we supplemented with (i) imidacloprid (0.375 ng·μl⁻¹), (ii) Ahiflower® oil (5 %) + imidacloprid (0.375 ng·μl⁻¹), and (iii) Ahiflower® oil (5 %). Survival was recorded, and after 21 days, worker bees were sampled to measure mitochondrial respiration, ATP5A1 content, adenylate energy charge, lipid peroxidation in thorax as well as fatty acid composition and peroxidation index in whole bees. Our results indicate that (i) imidacloprid mostly hampers mitochondria, increases saturated fatty acids and decreases survival, (ii) oxidation of alternative substrates allows full recovery of mitochondrial respiration in the imidacloprid-treated group demonstrating mitochondrial flexibility, (iii) Ahiflower® oil in combination with imidacloprid partially restores mitochondrial respiration at the level of complexes I and II, restores fatty acid composition but fails to restore survival. These findings confirm the deleterious effects of imidacloprid on mitochondria while highlighting, for the first time, the potential benefits of Ahiflower® oil in mitochondrial function, though not on honey bee survival. In addition, this study highlights the importance of mitochondrial flexibility when organisms are exposed to toxicants at environmentally relevant levels.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"296 ","pages":"Article 110238"},"PeriodicalIF":3.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172807","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":"Study on the alleviation of reactive oxygen species-mediated flunitrazepam toxicity in zebrafish (Danio rerio) by vitamin C and its mechanism","authors":"Qiuyu Liu ,&nbsp;Chuxiao Hu ,&nbsp;Xinqin Li ,&nbsp;Qiulan Liu ,&nbsp;Wenjie Xia ,&nbsp;Yuan Ren","doi":"10.1016/j.cbpc.2025.110237","DOIUrl":"10.1016/j.cbpc.2025.110237","url":null,"abstract":"<div><div>The frequent detection of psychoactive drugs in aquatic environments has caused various toxic effects on aquatic organisms, highlighting the urgent need to explore remediation methods and mechanisms. Against the backdrop of toxicity induced by the typical benzodiazepine (BZD) flunitrazepam (FLZ) in zebrafish, this study evaluates the mitigating effects of vitamin C (VC) on FLZ-induced embryonic developmental toxicity, larval behavioral anomalies, apoptosis, oxidative stress, and mitochondrial dysfunction at environmentally relevant concentrations through reactive oxygen species (ROS)-mediated pathways. Furthermore, molecular dynamics simulations were utilized to decipher the mechanism underlying ROS inhibition. Results demonstrated that co-exposure to 0.5 μg/L VC with FLZ (0.05 μg/L and 0.2 μg/L) significantly elevated the hatching rate of zebrafish embryos at 72 hpf and decreased the larval malformation rate at 96 hpf. In terms of physiological and biochemical indicators, VC significantly inhibited the FLZ-induced increase in ROS and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels. VC also upregulated the activity of mitochondrial uncoupling protein 2 (UCP2), a key regulator of ROS production. Molecular docking and dynamics simulations revealed that VC competitively binds to the LYS 38 and LYS 240 sites of UCP2, destabilizing FLZ-UCP2 interactions via steric hindrance and hydrogen bond competition. With the restoration of UCP2 activity, its proton leak function was enhanced, suppressing excessive ROS generation. Consequently, <em>uqcr2b</em>, <em>cox4i1l</em>, and <em>atp5g3b</em> were normalized, restoring ATP synthesis capacity and significantly alleviating FLZ-induced mitochondrial dysfunction. This study elucidates the mechanism by which VC counteracts ROS-mediated FLZ toxicity, providing critical insights for assessing environmental risks and formulating protective strategies against pollutants.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"296 ","pages":"Article 110237"},"PeriodicalIF":3.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168930","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":"Assessing the toxicity of bongkrekic acid in zebrafish embryos","authors":"Jiun-Lin Horng ,&nbsp;Kuan-Yi Lee ,&nbsp;Jen-Leih Wu ,&nbsp;Li-Yih Lin","doi":"10.1016/j.cbpc.2025.110235","DOIUrl":"10.1016/j.cbpc.2025.110235","url":null,"abstract":"<div><div>Bongkrekic acid (BA) is a potent bacterial toxin found in certain fermented foods, which poses a serious risk to human health through rapid multi-organ failure. Its toxic effects on the early stage of vertebrates remain poorly understood. In this study, we addressed this gap using zebrafish embryos as a model to evaluate BA's developmental toxicity. Following 96-h exposure to BA at concentrations of 0.01, 0.05, 0.1, and 1 mg/L, mortality rates increased sharply between 0.05 mg/L (25 %) and 0.1 mg/L (79 %). Morphological assessments at BA concentrations ≥0.1 mg/L revealed significant reductions in body length, eye and lens areas, and otic vesicle and otolith areas, as well as an enlarged yolk sac, indicating disrupted development and impaired nutrient utilization. Concentrations of BA of ≥0.05 mg/L induced bradycardia, hypo-contractility, and a larger ventricular volume, indicative of cardiotoxicity. BA at ≥0.05 mg/L reduced response rates in sensorimotor assessments and decreased neuromast hair cell numbers, suggesting neurobehavioral impairment. BA at ≥0.1 mg/L also induced hepatotoxicity, marked by reductions in liver area and EGFP fluorescence, along with signs of metabolic acidosis. Additionally, reductions in the mitochondrial-rich ionocyte density at ≥0.1 mg/L suggested compromised ion regulation. A histopathological examination revealed damage to critical organs, including the brain, eyes, and liver. These findings illustrate BA's multifaceted toxicity in embryos, impacting cardiac, neurobehavioral, liver metabolic, and ion regulatory functions.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"296 ","pages":"Article 110235"},"PeriodicalIF":3.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168931","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}