Pub Date : 2026-02-01Epub Date: 2025-11-28DOI: 10.1016/j.cbpc.2025.110415
Laura E. Hernández-Aguirre , Laura Camacho-Jiménez , Alma B. Peregrino-Uriarte , Gloria Yepiz-Plascencia
Polycyclic aromatic hydrocarbons (PAHs) are persistent organic pollutants that pose a significant risk to aquatic ecosystems. This study evaluated metabolic responses in hepatopancreas, focusing on key enzymes of glycolysis and anaerobic glycolysis in the shrimp Penaeus vannamei exposed for 24 and 96 h to phenanthrene (PHE) and naphthalene (NAP). We analyzed the expression of two hexokinase genes (HK1 and HK2), and lactate dehydrogenase (LDH1 and LDH2 subunits), total enzymatic activity of HK and LDH, and intracellular glucose and lactate. NAP significantly induced the expression of HKs and LDHs at 96 h, while PHE had no significant effect. LDH2 expression was detected only in response to NAP, suggesting that this PAH enhances anaerobic metabolism, possibly due to a higher oxygen demand for NAP detoxification. Although no significant differences were detected in the total activities of HK and LDH due to exposure to the selected PAHs, a decreasing trend was detected in HK activity under NAP treatment at 24 h. Additionally, glucose decreased over time. In contrast, lactate levels increased at 24 h in response to NAP and PHE, suggesting an early shift toward anaerobic metabolism, and then returned to initial levels by 96 h. These findings highlight the effects of PAHs on energy metabolism disruption in shrimp and provide insights into the molecular responses of aquatic invertebrates to metabolic stress induced by organic pollutants.
{"title":"The polycyclic aromatic hydrocarbons phenanthrene and naphthalene affect differentially key glycolytic enzymes in the whiteleg shrimp Penaeus vannamei","authors":"Laura E. Hernández-Aguirre , Laura Camacho-Jiménez , Alma B. Peregrino-Uriarte , Gloria Yepiz-Plascencia","doi":"10.1016/j.cbpc.2025.110415","DOIUrl":"10.1016/j.cbpc.2025.110415","url":null,"abstract":"<div><div>Polycyclic aromatic hydrocarbons (PAHs) are persistent organic pollutants that pose a significant risk to aquatic ecosystems. This study evaluated metabolic responses in hepatopancreas, focusing on key enzymes of glycolysis and anaerobic glycolysis in the shrimp <em>Penaeus vannamei</em> exposed for 24 and 96 h to phenanthrene (PHE) and naphthalene (NAP). We analyzed the expression of two hexokinase genes (HK1 and HK2), and lactate dehydrogenase (LDH1 and LDH2 subunits), total enzymatic activity of HK and LDH, and intracellular glucose and lactate. NAP significantly induced the expression of HKs and LDHs at 96 h, while PHE had no significant effect. LDH2 expression was detected only in response to NAP, suggesting that this PAH enhances anaerobic metabolism, possibly due to a higher oxygen demand for NAP detoxification. Although no significant differences were detected in the total activities of HK and LDH due to exposure to the selected PAHs, a decreasing trend was detected in HK activity under NAP treatment at 24 h. Additionally, glucose decreased over time. In contrast, lactate levels increased at 24 h in response to NAP and PHE, suggesting an early shift toward anaerobic metabolism, and then returned to initial levels by 96 h. These findings highlight the effects of PAHs on energy metabolism disruption in shrimp and provide insights into the molecular responses of aquatic invertebrates to metabolic stress induced by organic pollutants.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110415"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647473","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 : 2026-02-01Epub Date: 2025-11-22DOI: 10.1016/j.cbpc.2025.110395
Ruo-Yu Zhou , Lu Chen , Meng-Yang Hu, Mu-Xi Li, Yu-Xuan Fei, Mei Huang, Yun-Long Zhang
Ammonia is a common environmental pollutant that is extremely toxic to aquatic animals. Therefore, there is an urgent need to increase ammonia tolerance in aquaculture animals to achieve high-quality development of the industry. Three treatments were designed to examine the effects of taurine on the large-scale loach (Paramisgurnus dabryanus). These were a control group (exposed to water and injected with physiological saline), an ammonia treatment group (exposed to 30 mmol/L NH4Cl solution and injected with physiological saline), and a taurine treatment group (exposed to 30 mmol/L NH4Cl solution and injected with taurine). Immune- and ammonia metabolism-related markers were measured at 12 h, 24 h, 48 h, and 96 h after treatment. The results showed that ammonia exposure significantly increased T-SOD activity and the level of IL-1β, significantly decreased IgM, C3, and TNF-α levels, and induced significantly high expression of immune-related genes (lyz, hsp70, tlr5, and myd88) in tissues. Intraperitoneal injection of taurine mitigated ammonia-induced disturbances in plasma glucose and osmotic pressure by regulating glucose metabolism and osmotic pressure balance. The results suggest that ammonia stress causes significant immune stimulation in large-scale loaches, and that taurine could alleviate this effect. Exposure to ammonia increases the concentration of ammonia in the gut, liver, kidneys, and gills of large-scale loach, significantly increases GDH and GS activity, and upregulates the expression levels of ammonia transporter-related genes such as aqps and rh. After taurine treatment, the concentration of ammonia in the somatic tissues of large-scale loaches significantly decreased, while the expression of ammonia transporter-related genes was inhibited, and the activities of GS was further enhanced. This indicates that large-scale loach initiate glutamine synthesis and upregulate ammonia transporter proteins to cope with the stress of highly concentrated ammonia, and that taurine can promote glutamine synthesis to decrease the in vivo ammonia concentration. The results can deepen our understanding of the toxicological effects of ammonia and the mechanisms by which taurine promotes ammonia tolerance in fishes, offering a basis for taurine application in aquaculture.
{"title":"Effects of taurine on immunity and ammonia metabolism in large-scale loach under ammonia stress","authors":"Ruo-Yu Zhou , Lu Chen , Meng-Yang Hu, Mu-Xi Li, Yu-Xuan Fei, Mei Huang, Yun-Long Zhang","doi":"10.1016/j.cbpc.2025.110395","DOIUrl":"10.1016/j.cbpc.2025.110395","url":null,"abstract":"<div><div>Ammonia is a common environmental pollutant that is extremely toxic to aquatic animals. Therefore, there is an urgent need to increase ammonia tolerance in aquaculture animals to achieve high-quality development of the industry. Three treatments were designed to examine the effects of taurine on the large-scale loach (<em>Paramisgurnus dabryanus</em>). These were a control group (exposed to water and injected with physiological saline), an ammonia treatment group (exposed to 30 mmol/L NH<sub>4</sub>Cl solution and injected with physiological saline), and a taurine treatment group (exposed to 30 mmol/L NH<sub>4</sub>Cl solution and injected with taurine). Immune- and ammonia metabolism-related markers were measured at 12 h, 24 h, 48 h, and 96 h after treatment. The results showed that ammonia exposure significantly increased T-SOD activity and the level of IL-1β, significantly decreased IgM, C3, and TNF-α levels, and induced significantly high expression of immune-related genes (<em>lyz</em>, <em>hsp70</em>, <em>tlr5</em>, and <em>myd88</em>) in tissues. Intraperitoneal injection of taurine mitigated ammonia-induced disturbances in plasma glucose and osmotic pressure by regulating glucose metabolism and osmotic pressure balance. The results suggest that ammonia stress causes significant immune stimulation in large-scale loaches, and that taurine could alleviate this effect. Exposure to ammonia increases the concentration of ammonia in the gut, liver, kidneys, and gills of large-scale loach, significantly increases GDH and GS activity, and upregulates the expression levels of ammonia transporter-related genes such as <em>aqps</em> and <em>rh</em>. After taurine treatment, the concentration of ammonia in the somatic tissues of large-scale loaches significantly decreased, while the expression of ammonia transporter-related genes was inhibited, and the activities of GS was further enhanced. This indicates that large-scale loach initiate glutamine synthesis and upregulate ammonia transporter proteins to cope with the stress of highly concentrated ammonia, and that taurine can promote glutamine synthesis to decrease the in vivo ammonia concentration. The results can deepen our understanding of the toxicological effects of ammonia and the mechanisms by which taurine promotes ammonia tolerance in fishes, offering a basis for taurine application in aquaculture.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110395"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596069","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 : 2026-02-01Epub Date: 2025-10-31DOI: 10.1016/j.cbpc.2025.110385
Gil Martins , Sunil Poudel , Ana Portela , Gonçalo Pinto , Tamára F. Santos , Francisco A. Guardiola , Ana Marreiros , Paulo J. Gavaia
Zebrafish is a relevant model in skeletal research, enabling insights into bone development and regeneration. Inflammation supports tissue regeneration; however, excessive or chronic inflammation can delay the healing process and contribute to the development of skeletal disorders. Bacterial infections or LPS exposure exacerbate inflammation, hindering bone regeneration. Here, we tested the effects of LPS (1 and 10 μg/mL) as an inducer of an inflammatory response and evaluated its impact on the bone using zebrafish regenerating scales as a model. Results showed that exposure to LPS leads to an inflammatory process that affects scale regenerative ability. Exposure to LPS (10 μg/mL) led to a reduction in scale area, increased scale aspect ratio, osteoclast activity with scale demineralization, as well as overexpression of osteoclastic markers (acp5 and oc-stamp) and downregulation of the osteoblastic marker sp7. Our data suggest that zebrafish regenerating scales exposed to LPS can be further developed as an in vivo screening method to elucidate the mechanisms involved in the increased bone resorption associated with inflammatory processes, to evaluate the effects on osteoblast-osteoclast interaction in fish, and to search for novel therapeutic compounds for skeletal disorders and diseases.
{"title":"Lipopolysaccharides increase the resorption levels and affect zebrafish scales de novo bone formation","authors":"Gil Martins , Sunil Poudel , Ana Portela , Gonçalo Pinto , Tamára F. Santos , Francisco A. Guardiola , Ana Marreiros , Paulo J. Gavaia","doi":"10.1016/j.cbpc.2025.110385","DOIUrl":"10.1016/j.cbpc.2025.110385","url":null,"abstract":"<div><div>Zebrafish is a relevant model in skeletal research, enabling insights into bone development and regeneration. Inflammation supports tissue regeneration; however, excessive or chronic inflammation can delay the healing process and contribute to the development of skeletal disorders. Bacterial infections or LPS exposure exacerbate inflammation, hindering bone regeneration. Here, we tested the effects of LPS (1 and 10 μg/mL) as an inducer of an inflammatory response and evaluated its impact on the bone using zebrafish regenerating scales as a model. Results showed that exposure to LPS leads to an inflammatory process that affects scale regenerative ability. Exposure to LPS (10 μg/mL) led to a reduction in scale area, increased scale aspect ratio, osteoclast activity with scale demineralization, as well as overexpression of osteoclastic markers (<em>acp5</em> and <em>oc-stamp</em>) and downregulation of the osteoblastic marker <em>sp7</em>. Our data suggest that zebrafish regenerating scales exposed to LPS can be further developed as an <em>in vivo</em> screening method to elucidate the mechanisms involved in the increased bone resorption associated with inflammatory processes, to evaluate the effects on osteoblast-osteoclast interaction in fish, and to search for novel therapeutic compounds for skeletal disorders and diseases.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110385"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430118","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 : 2026-02-01Epub Date: 2025-11-19DOI: 10.1016/j.cbpc.2025.110399
Yahui Wu , Qing Huang
Astaxanthin (AST) as a natural carotenoid exhibits potent antioxidant and anti-inflammatory capacities. This work investigated AST’s protective effects against microcystin-LR (MC-LR) toxicity to zebrafish embryos. When the zebrafish embryos were exposed to a sublethal, environmentally relevant concentration of MC-LR (10 μg/L, approximately half of the LC50 value), AST (100 μg/L) could significantly reduce MC-LR-induced mortality by 39.8% and deformity rates by 60.0%. Furthermore, AST decreased ROS and MDA levels by 11.0% and 14.5%, respectively, and enhanced the activities of superoxide dismutase (SOD, 4.4-fold), catalase (CAT, 1.2-fold), and glutathione reductase (GR, 1.6-fold). It also ameliorated MC-LR-induced inflammatory responses, as evidenced by a 49.1% reduction in neutral red staining, a 42.0% to 42.9% improvement in host resistance, and a significant down-regulation of major cytokines (IL-1β, IL-6, IL-8, TNF-α) by 0.4 to 0.6-fold. Analysis of the transcriptome revealed that AST can inhibit the C-type lectin receptor signaling pathway and others to counteract the inflammatory and oxidative stress induced by MC-LR. Our findings confirm that AST neutralizes the toxicity of MC-LR through the mechanisms of antagonizing oxidative stress, exhibiting anti-inflammatory and immunomodulatory effects, which may pave the way for AST being used in aquaculture and environmental health.
{"title":"Astaxanthin mitigates the inflammatory toxicity of microcystin-LR on zebrafish embryos","authors":"Yahui Wu , Qing Huang","doi":"10.1016/j.cbpc.2025.110399","DOIUrl":"10.1016/j.cbpc.2025.110399","url":null,"abstract":"<div><div>Astaxanthin (AST) as a natural carotenoid exhibits potent antioxidant and anti-inflammatory capacities. This work investigated AST’s protective effects against microcystin-LR (MC-LR) toxicity to zebrafish embryos. When the zebrafish embryos were exposed to a sublethal, environmentally relevant concentration of MC-LR (10 μg/L, approximately half of the LC<sub>50</sub> value), AST (100 μg/L) could significantly reduce MC-LR-induced mortality by 39.8% and deformity rates by 60.0%. Furthermore, AST decreased ROS and MDA levels by 11.0% and 14.5%, respectively, and enhanced the activities of superoxide dismutase (SOD, 4.4-fold), catalase (CAT, 1.2-fold), and glutathione reductase (GR, 1.6-fold). It also ameliorated MC-LR-induced inflammatory responses, as evidenced by a 49.1% reduction in neutral red staining, a 42.0% to 42.9% improvement in host resistance, and a significant down-regulation of major cytokines (IL-1β, IL-6, IL-8, TNF-α) by 0.4 to 0.6-fold. Analysis of the transcriptome revealed that AST can inhibit the C-type lectin receptor signaling pathway and others to counteract the inflammatory and oxidative stress induced by MC-LR. Our findings confirm that AST neutralizes the toxicity of MC-LR through the mechanisms of antagonizing oxidative stress, exhibiting anti-inflammatory and immunomodulatory effects, which may pave the way for AST being used in aquaculture and environmental health.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110399"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573364","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 : 2026-02-01Epub Date: 2025-11-22DOI: 10.1016/j.cbpc.2025.110401
Cameron M. Emadi , Fabio Dos Santos Neto , Jason R. Bohenek , Breana Smithers , Miguel F. Acevedo , Edward M. Mager
Macrobrachium rosenbergii, the giant freshwater prawn, is an important aquaculture species cultivated worldwide. As a catadromous species, it requires brackish water for early development (larval stages) and grows optimally under low-salinity conditions. This tolerance enables production using brackish groundwater or desalination concentrate, helping reduce disposal costs. However, aquaculture systems often accumulate nitrogenous waste such as ammonia, which can negatively affect growth, survival, and health. The interactive effects of ammonia and salinity on M. rosenbergii remained understudied, particularly during juvenile stages that coincide with the transition to brackish water. Therefore, we first determined the 3, 6, 24, and 48 h median lethal concentrations (LC50) of total ammonia nitrogen (TAN) across three salinities (1, 5, and 10 ppt) at pH 8.2. Toxicity increased with both salinity and exposure time, with LC50 values ranging from 5.6 mg/L (95 % CI: 4.9–6.3) to 42 mg/L (95 % CI: 37–48) TAN. Based on these LC50 values, we tested how increasing waterborne ammonia concentrations affect the routine metabolic rate (RMR) of juvenile M. rosenbergii using static intermittent respirometry. Analysis by a linear mixed-effects model revealed a significant salinity × ammonia interaction where the positive relationship between ammonia concentration and RMR became steeper at higher salinities. The model also identified a significant main effect of ammonia, with RMR increasing as ammonia concentration rose, but no significant main effect of salinity. These findings inform aquaculture management of M. rosenbergii and demonstrate the potential for sentinel respirometry systems to detect real-time water quality changes by monitoring metabolic rates.
{"title":"Acute toxicity assessment and real-time metabolic rate responses of early life stage Macrobrachium rosenbergii to ammonia exposures at different salinities","authors":"Cameron M. Emadi , Fabio Dos Santos Neto , Jason R. Bohenek , Breana Smithers , Miguel F. Acevedo , Edward M. Mager","doi":"10.1016/j.cbpc.2025.110401","DOIUrl":"10.1016/j.cbpc.2025.110401","url":null,"abstract":"<div><div><em>Macrobrachium rosenbergii</em>, the giant freshwater prawn, is an important aquaculture species cultivated worldwide. As a catadromous species, it requires brackish water for early development (larval stages) and grows optimally under low-salinity conditions. This tolerance enables production using brackish groundwater or desalination concentrate, helping reduce disposal costs. However, aquaculture systems often accumulate nitrogenous waste such as ammonia, which can negatively affect growth, survival, and health. The interactive effects of ammonia and salinity on <em>M. rosenbergii</em> remained understudied, particularly during juvenile stages that coincide with the transition to brackish water. Therefore, we first determined the 3, 6, 24, and 48 h median lethal concentrations (LC<sub>50</sub>) of total ammonia nitrogen (TAN) across three salinities (1, 5, and 10 ppt) at pH 8.2. Toxicity increased with both salinity and exposure time, with LC<sub>50</sub> values ranging from 5.6 mg/L (95 % CI: 4.9–6.3) to 42 mg/L (95 % CI: 37–48) TAN. Based on these LC<sub>50</sub> values, we tested how increasing waterborne ammonia concentrations affect the routine metabolic rate (RMR) of juvenile <em>M. rosenbergii</em> using static intermittent respirometry. Analysis by a linear mixed-effects model revealed a significant salinity × ammonia interaction where the positive relationship between ammonia concentration and RMR became steeper at higher salinities. The model also identified a significant main effect of ammonia, with RMR increasing as ammonia concentration rose, but no significant main effect of salinity. These findings inform aquaculture management of <em>M. rosenbergii</em> and demonstrate the potential for sentinel respirometry systems to detect real-time water quality changes by monitoring metabolic rates.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110401"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596032","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 : 2026-02-01Epub Date: 2025-11-23DOI: 10.1016/j.cbpc.2025.110402
Abdul Haleem Khan , Muhammad Jawad , Sana Nasir , Haijing Xu , Mengzhou Wu , Junqiang Qiu , Mingyou Li
Copper (Cu2+), though essential as a micronutrient, can pose significant ecotoxicological risks when introduced into aquatic environments at elevated levels, primarily due to anthropogenic sources such as industrial discharge, agricultural runoff, and urban effluents. This study investigated the long-term effects of environmentally relevant copper concentrations (0, 5, 10, and 20 μg/L) on Japanese medaka (Oryzias latipes) over a six-month exposure period, focusing on reproductive toxicity, oxidative stress, immune response, and gut microbiota alterations. Histopathological analysis revealed gonadal impairments, including disrupted testicular and ovarian structures, impaired spermatogenesis, and reduced oocyte maturation. Additionally, hormonal changes revealed elevated levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2), alongside reduced testosterone (T) levels, indicating interference with the hypothalamic–pituitary–gonadal (HPG) axis. Copper exposure also altered antioxidant enzyme activities, including sex-dependent modulation of superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels, indicating oxidative imbalance and compensatory defense responses, along with upregulation of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). Gut microbiota analysis via 16S rRNA sequencing revealed significant dysbiosis, characterized by marked reductions in alpha diversity indices and distinct beta diversity clustering. Taxonomic profiling showed a sharp decline in beneficial phyla such as Fusobacteriota, Firmicutes, and Actinobacteriota, coupled with an enrichment of potentially opportunistic Proteobacteria and shifts in Bacteroidota and Verrucomicrobiota, indicating compromised intestinal homeostasis. Collectively, these findings demonstrate that chronic exposure to copper ions induces multi-systemic toxicity in O. latipes, impairing reproductive function, provoking oxidative and inflammatory responses, and reshaping gut microbial communities in ways that may exacerbate host physiological stress.
{"title":"Chronic copper exposure induces multi-systemic toxicity in Japanese medaka (Oryzias latipes) via reproductive disruption, and gut microbiota dysbiosis","authors":"Abdul Haleem Khan , Muhammad Jawad , Sana Nasir , Haijing Xu , Mengzhou Wu , Junqiang Qiu , Mingyou Li","doi":"10.1016/j.cbpc.2025.110402","DOIUrl":"10.1016/j.cbpc.2025.110402","url":null,"abstract":"<div><div>Copper (Cu<sup>2+</sup>), though essential as a micronutrient, can pose significant ecotoxicological risks when introduced into aquatic environments at elevated levels, primarily due to anthropogenic sources such as industrial discharge, agricultural runoff, and urban effluents. This study investigated the long-term effects of environmentally relevant copper concentrations (0, 5, 10, and 20 μg/L) on Japanese medaka (<em>Oryzias latipes</em>) over a six-month exposure period, focusing on reproductive toxicity, oxidative stress, immune response, and gut microbiota alterations. Histopathological analysis revealed gonadal impairments, including disrupted testicular and ovarian structures, impaired spermatogenesis, and reduced oocyte maturation. Additionally, hormonal changes revealed elevated levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2), alongside reduced testosterone (T) levels, indicating interference with the hypothalamic–pituitary–gonadal (HPG) axis. Copper exposure also altered antioxidant enzyme activities, including sex-dependent modulation of superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels, indicating oxidative imbalance and compensatory defense responses, along with upregulation of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). Gut microbiota analysis via 16S rRNA sequencing revealed significant dysbiosis, characterized by marked reductions in alpha diversity indices and distinct beta diversity clustering. Taxonomic profiling showed a sharp decline in beneficial phyla such as Fusobacteriota, Firmicutes, and Actinobacteriota, coupled with an enrichment of potentially opportunistic <em>Proteobacteria</em> and shifts in <em>Bacteroidota</em> and <em>Verrucomicrobiota</em>, indicating compromised intestinal homeostasis. Collectively, these findings demonstrate that chronic exposure to copper ions induces multi-systemic toxicity in <em>O. latipes</em>, impairing reproductive function, provoking oxidative and inflammatory responses, and reshaping gut microbial communities in ways that may exacerbate host physiological stress.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110402"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145602794","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 : 2026-02-01Epub Date: 2025-10-31DOI: 10.1016/j.cbpc.2025.110382
Helei Cai , Qizhuan Lin , Changyong Gong , Fan Yu , Libo Jin , Renyi Peng
Per-and polyfluoroalkyl substances (PFAS) are widely distributed across freshwater systems in mainland China, with concentrations showing marked spatial heterogeneity—particularly in eastern regions with intensive industrial activity. Fish not only play a vital ecological role but also serve as an important source of protein for humans. Due to the biomagnification factors (BMF > 1) of PFAS in the food chain, the risk of exposure increases for high-trophic-level fish, other predators, and ultimately humans. Co-exposure with other environmental pollutants further amplifies PFAS-induced immunotoxic effects. The immunotoxicity of PFAS is influenced by carbon chain length and functional groups, with long-chain PFAS and sulfonic acid groups generally exhibiting stronger immunotoxic effects in fish. These compounds significantly suppress both innate and adaptive immune responses by interfering with Toll-like receptor signaling pathways, inducing oxidative stress, and impairing immune cell function. Although current technologies are available for PFAS removal, they still face considerable limitations and challenges. This review summarizes the characteristics and spatial distribution of PFAS contamination in mainland China's aquatic environments and focuses on the mechanisms of PFAS-induced immunotoxicity in fish. It offers valuable insights for future research into the synergistic/antagonistic and time-dependent effects of combined PFAS and multi-pollutant exposure. Moreover, it provides important references for the development of mitigation technologies targeting PFAS-related ecotoxicity in aquatic food chains and for informing relevant policy formulation.
{"title":"PFAS-induced immunotoxicity in freshwater fish of inland China: mechanisms and ecological risks","authors":"Helei Cai , Qizhuan Lin , Changyong Gong , Fan Yu , Libo Jin , Renyi Peng","doi":"10.1016/j.cbpc.2025.110382","DOIUrl":"10.1016/j.cbpc.2025.110382","url":null,"abstract":"<div><div><em>Per</em>-and polyfluoroalkyl substances (PFAS) are widely distributed across freshwater systems in mainland China, with concentrations showing marked spatial heterogeneity—particularly in eastern regions with intensive industrial activity. Fish not only play a vital ecological role but also serve as an important source of protein for humans. Due to the biomagnification factors (BMF > 1) of PFAS in the food chain, the risk of exposure increases for high-trophic-level fish, other predators, and ultimately humans. Co-exposure with other environmental pollutants further amplifies PFAS-induced immunotoxic effects. The immunotoxicity of PFAS is influenced by carbon chain length and functional groups, with long-chain PFAS and sulfonic acid groups generally exhibiting stronger immunotoxic effects in fish. These compounds significantly suppress both innate and adaptive immune responses by interfering with Toll-like receptor signaling pathways, inducing oxidative stress, and impairing immune cell function. Although current technologies are available for PFAS removal, they still face considerable limitations and challenges. This review summarizes the characteristics and spatial distribution of PFAS contamination in mainland China's aquatic environments and focuses on the mechanisms of PFAS-induced immunotoxicity in fish. It offers valuable insights for future research into the synergistic/antagonistic and time-dependent effects of combined PFAS and multi-pollutant exposure. Moreover, it provides important references for the development of mitigation technologies targeting PFAS-related ecotoxicity in aquatic food chains and for informing relevant policy formulation.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110382"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430167","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 : 2026-02-01Epub Date: 2025-11-14DOI: 10.1016/j.cbpc.2025.110389
Luana Granada , Inês F.C. Morão , Marco F.L. Lemos , Peter Bossier , Sara C. Novais
The rotifer Brachionus sp. is of great importance for aquaculture, as the reproduction cycle under rearing conditions of many economically important species larvae depends on the use of rotifers as first live feed. Establishing a protocol that results in an improved tolerance of rotifers to environmental stressors will allow for a more stable rotifer production. The exposure to non-lethal heat shocks (NLHS) already proved to enhance the tolerance, not only to heat stress, but also to other stressors in several aquatic species, by activating the heat shock response and epigenetic mechanisms. This study aimed to determine the potential of a single NLHS to induce tolerance to different abiotic stressors in two strains of B. koreanus (MRS10 and IBA3) and to evaluate possible molecular mechanisms involved in the achievement of increased tolerance to hydrogen peroxide induced by NLHS. Cross-tolerance was achieved for both strains, namely to high salinity, cadmium chloride, and hydrogen peroxide. Scale-up tests resulted in increased tolerance to hydrogen peroxide only for MRS10. During the exposure to this substance, heat-shocked MRS10 rotifers showed an up-regulation of genes related to oxidative stress response and histone modifications, increased production of HSP70, and higher levels of total acetylation of histone H3. A single NLHS proved to induce epigenetic effects when rotifers were exposed to other stressor later in life. However, further studies should elucidate if the NLHS conditions used in this study can yield a persistent outcome, allowing the establishment of tolerant rotifer strain lines and, consequently, a more stable production.
{"title":"Non-lethal heat shock induces cross-tolerance to different stressors in two strains of Brachionus koreanus (Rotifera: Monogononta): Mechanisms of increased tolerance to hydrogen peroxide","authors":"Luana Granada , Inês F.C. Morão , Marco F.L. Lemos , Peter Bossier , Sara C. Novais","doi":"10.1016/j.cbpc.2025.110389","DOIUrl":"10.1016/j.cbpc.2025.110389","url":null,"abstract":"<div><div>The rotifer <em>Brachionus</em> sp. is of great importance for aquaculture, as the reproduction cycle under rearing conditions of many economically important species larvae depends on the use of rotifers as first live feed. Establishing a protocol that results in an improved tolerance of rotifers to environmental stressors will allow for a more stable rotifer production. The exposure to non-lethal heat shocks (NLHS) already proved to enhance the tolerance, not only to heat stress, but also to other stressors in several aquatic species, by activating the heat shock response and epigenetic mechanisms. This study aimed to determine the potential of a single NLHS to induce tolerance to different abiotic stressors in two strains of <em>B. koreanus</em> (MRS10 and IBA3) and to evaluate possible molecular mechanisms involved in the achievement of increased tolerance to hydrogen peroxide induced by NLHS. Cross-tolerance was achieved for both strains, namely to high salinity, cadmium chloride, and hydrogen peroxide. Scale-up tests resulted in increased tolerance to hydrogen peroxide only for MRS10. During the exposure to this substance, heat-shocked MRS10 rotifers showed an up-regulation of genes related to oxidative stress response and histone modifications, increased production of HSP70, and higher levels of total acetylation of histone H3. A single NLHS proved to induce epigenetic effects when rotifers were exposed to other stressor later in life. However, further studies should elucidate if the NLHS conditions used in this study can yield a persistent outcome, allowing the establishment of tolerant rotifer strain lines and, consequently, a more stable production.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110389"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534408","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 : 2026-02-01Epub Date: 2025-11-23DOI: 10.1016/j.cbpc.2025.110403
Yuanhua Wang , Jie Ren , Siling Zhang , Hao Xu
The tire-derived antioxidant 6PPD (N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine), a ubiquitous environmental contaminant, poses significant risks to aquatic ecosystems, yet its sex-specific physiological impacts remain underexplored. This study investigated the effects of environmentally relevant 6PPD concentrations (20 μg/L) on feeding, digestion, absorption, and reproduction in adult zebrafish over 28 days. Results revealed pronounced male-specific impairments: 6PPD-exposed males exhibited reduced feeding speed and maximum food intake, alongside suppressed locomotor responses to food stimuli. Mechanistically, upregulation of intestinal cholecystokinin b (cckb) and delayed intestinal content emptying were identified as potential drivers of feeding inhibition in males. Concurrently, 6PPD induced intestinal oxidative stress in males, manifested through decreased activities of catalase (CAT) and superoxide dismutase (SOD), alongside elevated malondialdehyde (MDA) levels, and activated ferroptosis via dysregulation of critical genes (gpx4a, cybb, slc7a11, hmox1a, tfr1b and trf2). These disruptions correlated with shortened intestinal villi, goblet cell loss, and impaired nutrient absorption, leading to increased fecal output and diminished growth performance in males. In contrast, females displayed no significant structural damage to intestinal epithelium or declines in digestive and absorptive capacities. Notably, 6PPD caused no gonadal histopathological changes, hormonal dysregulation, reduced fertilization and hatching rates, nor transgenerational effects such as developmental abnormalities or locomotor deficits in offspring. This study provides the first evidence of male-selective feeding suppression and intestinal toxicity induced by 6PPD, highlighting sex-dependent vulnerability in aquatic species and underscoring the need for gender-specific risk assessments of tire-derived pollutants.
{"title":"Sex-specific effects of 6PPD on adult zebrafish: male-selective feeding inhibition, nutrient malabsorption, intestinal epithelial damage, and absence of reproductive toxicity","authors":"Yuanhua Wang , Jie Ren , Siling Zhang , Hao Xu","doi":"10.1016/j.cbpc.2025.110403","DOIUrl":"10.1016/j.cbpc.2025.110403","url":null,"abstract":"<div><div>The tire-derived antioxidant 6PPD (N-(1,3-dimethylbutyl)-<em>N</em>′-phenyl-<em>p</em>-phenylenediamine), a ubiquitous environmental contaminant, poses significant risks to aquatic ecosystems, yet its sex-specific physiological impacts remain underexplored. This study investigated the effects of environmentally relevant 6PPD concentrations (20 μg/L) on feeding, digestion, absorption, and reproduction in adult zebrafish over 28 days. Results revealed pronounced male-specific impairments: 6PPD-exposed males exhibited reduced feeding speed and maximum food intake, alongside suppressed locomotor responses to food stimuli. Mechanistically, upregulation of intestinal cholecystokinin b (<em>cckb</em>) and delayed intestinal content emptying were identified as potential drivers of feeding inhibition in males. Concurrently, 6PPD induced intestinal oxidative stress in males, manifested through decreased activities of catalase (CAT) and superoxide dismutase (SOD), alongside elevated malondialdehyde (MDA) levels, and activated ferroptosis via dysregulation of critical genes (<em>gpx4a</em>, <em>cybb</em>, <em>slc7a11</em>, <em>hmox1a</em>, <em>tfr1b</em> and <em>trf2</em>). These disruptions correlated with shortened intestinal villi, goblet cell loss, and impaired nutrient absorption, leading to increased fecal output and diminished growth performance in males. In contrast, females displayed no significant structural damage to intestinal epithelium or declines in digestive and absorptive capacities. Notably, 6PPD caused no gonadal histopathological changes, hormonal dysregulation, reduced fertilization and hatching rates, nor transgenerational effects such as developmental abnormalities or locomotor deficits in offspring. This study provides the first evidence of male-selective feeding suppression and intestinal toxicity induced by 6PPD, highlighting sex-dependent vulnerability in aquatic species and underscoring the need for gender-specific risk assessments of tire-derived pollutants.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110403"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145602782","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 : 2026-02-01Epub Date: 2025-11-20DOI: 10.1016/j.cbpc.2025.110398
Sodikdjon A. Kodirov
The phenotype of action potentials (AP) in mammalian dorsal root ganglion (DRG) neurons is biphasic and thereby distinct from those in the CNS and spinal cord. The sensation of pain by DRG and its prevention may occur via many types of channels, receptors, and neurotransmitters; these are at least Cav, Kv, Nav, and TRP. The Cav, Kv, and Nav channels are prevailingly involved in the excitability of DRG neurons, while the TRP family enables the mechanosensitivity. The latter are the main family of channels, and thereby the list is extensive because of the presence of many distinct α subunits among them. Also, all major receptor channels are described in DRG, but purinergic ones could be considered important because of sensitization to ATP as a neurotransmitter. This work presents a comparative and detailed synthesis of the electrophysiological properties of intact DRG and isolated neurons, with an emphasis on the K channels involved in action potential generation.
{"title":"K channels and action potential in dorsal root ganglion of diverse animals","authors":"Sodikdjon A. Kodirov","doi":"10.1016/j.cbpc.2025.110398","DOIUrl":"10.1016/j.cbpc.2025.110398","url":null,"abstract":"<div><div>The phenotype of action potentials (AP) in mammalian dorsal root ganglion (DRG) neurons is biphasic and thereby distinct from those in the CNS and spinal cord. The sensation of pain by DRG and its prevention may occur via many types of channels, receptors, and neurotransmitters; these are at least Cav, Kv, Nav, and TRP. The Cav, Kv, and Nav channels are prevailingly involved in the excitability of DRG neurons, while the TRP family enables the mechanosensitivity. The latter are the main family of channels, and thereby the list is extensive because of the presence of many distinct α subunits among them. Also, all major receptor channels are described in DRG, but purinergic ones could be considered important because of sensitization to ATP as a neurotransmitter. This work presents a comparative and detailed synthesis of the electrophysiological properties of intact DRG and isolated neurons, with an emphasis on the K channels involved in action potential generation.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"300 ","pages":"Article 110398"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145581914","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}