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International Journal of Environmental Research and Public Health · 2020 ·Vol. 17 ·期 2 ·651 · IF 2.849

Evaluation of the Oxidative Stress Status in Zebrafish (Danio rerio) Liver Induced by Three Typical Organic UV Filters (BP-4, PABA and PBSA)

Xinxin Huang,Yuanyuan Li,Tantan Wang,Hui Liu,Jiaqi Shi,Xuesheng Zhang

Organic UV filters are a kind of emerging pollutants, which have been widely used in personal care products (PCPs). This study evaluated the effects of benzophenone-4 (BP-4), 4-aminobenzoic acid (PABA), and 2-phenylbenzimidazole-5-sulfonic acid (PBSA) on the selected indices of antioxidative responses in zebrafish (Danio rerio) liver. Zebrafish were exposed to two different doses (i.e., 0.5 and 5 mg L−1) of semi-static water with three individual compounds. Liver samples were collected on 7 and 14 days to analyze biochemical indicators, including superoxide dismutase (SOD), glutathione S-transferase (GST), reduced glutathione (GSH), and malondialdehyde (MDA). Oxidative stress occurred in zebrafish liver with significantly changed indicators during the whole exposure period. Different experimental groups could induce or inhibit the activity of antioxidant enzymes with varying degrees. With a prolonged exposure time and increased exposure dose, the hepatic lipid peroxidation was also obviously observed. Moreover, the toxicity order of three organic UV filters was analyzed using the integrated biomarker response (IBR) index and the results indicate that exposure to PABA for 7 days at 0.5 mg L−1and PBSA for 7 days at 5 mg L−1induced the most severe oxidative stress in the liver of zebrafish.Keywords:organic UV filters;oxidative stress;lipid peroxidation;integrated biomarker response;zebrafish

✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMOSPHERE · 2019 · IF 5.108

Triclosan-induced liver and brain injury in zebrafish (Danio rerio) via abnormal expression of miR-125 regulated by PKCα/Nrf2/p53 signaling pathways

Caihong Wang,Wenhao Huang,Jiebo Lin,Fang Fang,Xuedong Wang,Huili Wang

Triclosan (TCS) is widely used in personal care products, and its chronic exposure leads to severely toxic effects in zebrafish ( Danio rerio ). PKCα, Nrf2 and p53 are three important signaling pathways concerned with cell development. Herein, we speculated on and verified a novel TCS regulatory pathway: (1) TCS acted on GPER (G-protein-coupled estrogen receptor) to activate MAPK/ERK pathway, further resulting in the expression changes of protein kinase C (PKC) family; (2) PKC participated in Nrf2 phosphorylation; (3) The expression of miR-125b was regulated by Nrf2; and (4) The expression changes of related genes in the PKCs-Nrf2-ARE pathway showed the specificity of zebrafish tissue and organ. TCS exposure led to down-regulation of the Nrf2 and phosphorylated Nrf2(Ser40) protein in diencephalon nucleus, stratum marginale and stratum centrale areas in adult zebrafish brain. The phosphorylated Nrf2(Ser40) was mainly expressed in PGz area, while it was not the case for Nrf2. Both Nrf2 and phosphorylated Nrf2 were activated by TCS exposure; however, the changing trend of PKCs was opposite to that of Nrf2 in the liver. Both DAPI staining and Merge images demonstrated that TCS induced oxidative phosphorylation, and phosphorylated Nrf2 is translocated into the nucleus as the transcription factor to regulate gene transcription in liver and brain. Nrf2 over-expression increased accumulation of lipid droplets in yolk, brain and liver, resulting from the upregulation of pri-miR-125b1, pri-miR-125b3, but not pri-miR-125b2. These findings reveal the upstream regulation mechanism of miR-125b for TCS-induced fat-metabolism disorder from the regulatory perspective of the pri-miR-125b promoter region.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY · 2025 · IF 4.3

Toxic effects of combined exposure to carbamazepine and triclosan on adult zebrafish (Danio rerio): Insights into acute mortality, neurotransmitters, biochemical response, and histopathology

Jiangong Jiang,Shuxin Zhao,Xinjie Guo,Wenzhen Liu,Huixue Duan,Xinyuan Zhou,Rongyu Li,Yanhong Chang,Haiyang Yu,Xinxin Du,Xing Hu

As two representative pharmaceuticals and personal care products (PCPPs), carbamazepine (CBZ) and triclosan (TCS) are frequently detected in aquatic ecosystems worldwide, but their toxicological interactions remain unclear. This work evaluated the combined toxicity of CBZ and TCS to zebrafish ( Danio rerio ) in terms of acute mortality, biochemical response, and histopathology. The results showed that the 96-h acute toxicity interaction of CBZ and TCS fitted well to the concentration addition (CA) model, suggesting an additive effect. Compared with exposure to either CBZ or TCS alone, co-exposure to CBZ and TCS at equivalent toxic concentrations can lead to a profound increase in gamma-aminobutyric acid (GABA) and a reduction in acetylcholine (ACh) and acetylcholinesterase (AChE) levels. Compared with CBZ or TCS alone, the 21-day co-exposure to CBZ and TCS at the 2 % LC 50 aggravated oxidative stress and histopathological damage to the gills, brain, and liver. Overall, these findings provide a reference for the rational and complete assessment of the combined toxicity of the PPCPs to aquatic organisms.

CAS / MDL: 3380-34-5 298-46-4
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JOURNAL OF HAZARDOUS MATERIALS · 2025 · IF 11.3

Multi-omics insights into 6PPD- and 6PPDQ-induced gut-liver axis disruption and non-alcoholic fatty liver disease progression in zebrafish (Danio rerio)

Yu Feng,Hongyi Xian,Ruobing Bai,Zhiming Li,Hao Li,Long Zhang,Xiyun Huang,Yuji Huang,Boxuan Liang,Yanhong Deng,Xiaohong Yang,Xiaoqing Chen,Wenjie Yu,Li Yan,Da Chen,Xinguang Zhong,Zhenlie Huang

The pervasive environmental presence of N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) and its transformation product, 6PPD-quinone (6PPDQ), has raised concerns about their potential toxicity, yet their interactions with the gut microbiota at environmentally relevant concentrations remain poorly understood. Here, we investigated the effects of 6PPD and 6PPDQ on the gut-liver axis in zebrafish ( Danio rerio ). Zebrafish larvae exposed to 0.01, 1, and 100 μg/L of 6PPD or 6PPDQ for five days exhibited intestinal and hepatic developmental toxicity, including hepatic lipid accumulation and hepatomegaly. Adult zebrafish exposed for 21 days displayed compromised intestinal barrier integrity, gut dysbiosis, and lipidomic disturbances in the liver. Statistical analysis using the multi-response permutation procedure confirmed significant shifts in gut microbial community structure. Dysbiosis was characterized by reduced beneficial bacteria and an increase in pathogenic taxa, accompanied by elevated circulating lipopolysaccharide (LPS) and upregulated hepatic expression of lbp (LPS-binding receptor). Hepatic lipid accumulation resulted from increased triglyceride (TG) and total cholesterol synthesis, with lipidomics revealing distinct disruptions: 6PPD impaired phosphatidylinositol phosphate synthesis, while 6PPDQ affected TG homeostasis. Correlation analysis linked gut microbial shifts to hepatic lipid dysregulation. These findings suggest that 6PPD and 6PPDQ exposure disrupts gut-liver axis homeostasis, potentially driving non-alcoholic fatty liver disease development. This study underscores the need to integrate gut-liver-microbiota endpoints into environmental risk assessments for aquatic organisms.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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Foods · 2024 ·Vol. 13 ·期 17 ·2729 · IF 4.7

Antihyperglycemic, Antiaging, and L. brevis Growth-Promoting Activities of an Exopolysaccharide from Agrobacterium sp. FN01 (Galacan) Evaluated in a Zebrafish (Danio rerio) Model

Xiaoqing Xu,Lingling Du,Meng Wang,Ran Zhang,Junjie Shan,Yu Qiao,Qing Peng,Bo Shi

Agrobacteriumsp. are notable for their ability to produce substantial amounts of exopolysaccharides. Our study identified an exopolysaccharide (Galacan, 4982.327 kDa) fromAgrobacteriumsp. FN01. Galacan is a heteropolysaccharide primarily composed of glucose and galactose at a molar ratio of 25:1. The FT-IR results suggested that Galacan had typical absorption peaks of polysaccharide. The results of periodate oxidation, Smith degradation, and NMR confirmed the presence of structural units, such as β-D-Galp(→, →3)β-D-Galp(1→, →2,3)β-D-Glcp(1→, β-D-Glcp(1→, and →2)β-D-Glcp(1→. Galacan demonstrated significant biological activities. In experiments conducted with zebrafish, it facilitated the proliferation ofLactobacillus brevisin the intestinal tract, suggesting potential prebiotic properties. Moreover, in vivo studies revealed its antihyperglycemic effects, as evidenced by significant reductions in blood glucose levels and enhanced fluorescence intensity of pancreatic β cells in a streptozotocin (STZ)-induced hyperglycemic zebrafish model. Additionally, antiaging assays demonstrated Galacan’s ability to inhibit β-galactosidase activity and enhance telomerase activity in a hydrogen peroxide (HP)-induced aging zebrafish model. These findings emphasized the potential of Galacan as a natural prebiotic with promising applications in diabetes prevention and antiaging interventions.

✓ 已验证 DOI PubMed 高影响因子
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2025 · IF 6.1

Comparative analysis of the toxicological and histopathological impact of microplastic fibers and microbeads in exposure associated with dibutyl phthalate in zebrafish (Danio rerio)

Zhendong Zhou,Xianfu Zhao,Le Liang,Min Su,Weigang Sun,Jianxiang Shen,Zhongguan Jiang

Acting as emerging pollutants in freshwater ecosystems, microplastics and plasticizers may have toxicological and histopathological effects on aquatic organisms. However, the combined toxicity of microplastics and plasticizers as well as the toxicological differences among various microplastic shapes have been limitedly studied. To address these gaps, we conducted laboratory experiments using zebrafish ( Danio rerio, Hamilton 1822) to assess oxidative stress levels, lipid peroxidation, and pathological damage under both sole and combined exposure to microplastic fibers (MFs), microbeads (MBs), and dibutyl phthalate (DBP). Generally, our results demonstrated significantly toxicological response of fish livers and intestines to the sole and combined exposure to microplastics (MFs and MBs) and DBP. Specifically, in fish livers, MFs accounted for the highest increase in CAT and GST activity, with more severe swollen hepatocytes and vacuolization occurred. Similarly, we also recorded higher SOD activity and MDA content with the exposure to MFs in zebrafish intestines. In addition, the exposure to MFs incurred more severe changes in goblet cell reduction and hypervacuolisation in fish intestines. In summary, MFs exhibited more severe oxidative stress and pathological damage than MBs, which highlighted the importance of prioritizing MFs in environmental monitoring and examining the toxicity of MFs on laboratory studies.

CAS / MDL: 84-74-2
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ENVIRONMENTAL POLLUTION · 2023 · IF 8.9

Insights into spirotetramat-induced thyroid disruption during zebrafish (Danio rerio) larval development: An integrated approach with in vivo, in vitro, and in silico analyses

Fang Jiao,Hua Rong,Yang Zhao,Panfeng Wu,Yaohui Long,Jie Xu,Tao Zhao,Lingxi Han,Jun Wang,Huirong Yang

Spirotetramat (SPT), a tetronic acid-derived insecticide, is implicated in reproductive and lipid metabolism disorders, as well as developmental toxicity in fish. While these effects are documented, the precise mechanisms underlying its developmental toxicity are not fully elucidated. In this study, zebrafish embryos (2 h post-fertilization, hpf) were exposed to four concentrations of SPT (0, 60, 120, and 240 μg/L) until 21 dpf (days post-fertilization). We delved into the mechanisms by examining its potential disruption of the thyroid endocrine system, employing in vivo , in vitro , and in silico assays. The findings showed notable developmental disturbances, including reduced hatching rates, shortened body lengths, and decelerated heart rates. Additionally, there was an increase in malformations and a decline in locomotor activity. Detailed analyses revealed that SPT exposure led to elevated thyroid hormone levels, perturbed the hypothalamic-pituitary-thyroid (HPT) axis transcript levels, amplified deiodinase type I (Dio1) and deiodinase type II (Dio2) activities, and both transcriptionally and proteomically upregulated thyroid receptor beta (TRβ) in larvae. Techniques like molecular docking and surface plasmon resonance (SPR) confirmed SPT's affinity for TRβ, consistent with in vitro findings suggesting its antagonistic effect on the T3-TR complex. These insights emphasize the need for caution in using tetronic acid-derived insecticides.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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AQUATIC TOXICOLOGY · 2024 · IF 4.1

The combined neurotoxicity of DBP and nano-TiO2 in embryonic zebrafish (Danio rerio) revealed by oxidative activity, neuro-development genes expression and metabolomics changes

Haiyue Chen,Yingjia Wang,Hongwu Liang

Dibutyl phthalate (DBP) is a commonly used plasticizer that is frequently detected in water samples due to its widespread use. Titanium dioxide nanoparticles (n-TiO 2 ) have been found to enhance the harmful effects of organic contaminants by increasing their bioavailability in aquatic environments. However, the combined toxic effects of DBP and n-TiO 2 on aquatic organisms remain unclear. This study aimed to investigate the neurotoxicity of DBP and n-TiO 2 synergistic exposure during the early life stage of zebrafish. The results of the study revealed that co-exposure of DBP and n-TiO 2 led to an increase in deformities and a significant reduction in the active duration of zebrafish larvae. Furthermore, the co-exposure of DBP and n-TiO 2 resulted in elevated levels of oxidative stress and altered gene expression related to neurodevelopment and apoptosis. Notably, n-TiO 2 exacerbated the oxidative damage and apoptosis induced by DBP alone exposure. Additionally, co-exposure of the 1.0 mg/L DBP and n-TiO 2 significantly affected the expression of genes associated with neurodevelopment. Moreover, disturbances in amino acid metabolism and interference with lipid metabolism were observed as a result of DBP and n-TiO 2 co-exposure. In general, n-TiO 2 aggravated the neurotoxicity of DBP in the early life stage of zebrafish by increasing oxidative stress, apoptosis, and disrupting amino acid synthesis and lipid metabolism. Therefore, it is essential to consider the potential risks caused by DBP and nanomaterials co-existence in the aquatic environment.

CAS / MDL: 175606-05-0
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2023 · IF 6.8

Effects of microplastic exposure on the early developmental period and circadian rhythm of zebrafish (Danio rerio): A comparative study of polylactic acid and polyglycolic acid

Jialu Luan,Shuhui Zhang,Yixin Xu,Liang Wen,Xizeng Feng

Polyglycolic acid (PGA) is an emerging biodegradable plastic material. Together with polylactic acid (PLA), PGA is considered a suitable alternative to conventional plastics and has been widely used in biomedical and food packaging industries. However, degradable plastics continue to face the drawbacks of harsh degradation environment and long degradation time, and may harm the environment and the human body. Therefore, our study focused on assessing the effects of degradable microplastics PGA and PLA on the development and neurobehavior of zebrafish. The results showed that PGA and PLA had little effect on 3–10 hpf embryos. However, developmental stunting was observed in a100 mg/L PGA and PLA-exposed group at 24 hpf. In addition, PGA and PLA exposure decreased the survival and hatching rates, increased wakefulness, and reduced sleep in zebrafish. This indicates that PGA and PLA may affect the circadian behavior of zebrafish by affecting the brain–derived neurotrophic factor (BDNF). Therefore, our results suggest that PGA and PLA exposure induces developmental toxicity, reduces voluntary locomotion, induces of anxiety–like behaviors, and impairs sleep/wake behaviors in zebrafish larvae. This also suggests that the potentially toxic effects of degradable plastics cannot be ignored and that the biological effects of PGA require further research.

CAS / MDL: 38183-03-8
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SCIENCE OF THE TOTAL ENVIRONMENT · 2022 · IF 10.753

Environmentally relevant concentrations of butyl benzyl phthalate triggered oxidative stress and apoptosis in adult zebrafish (Danio rerio) liver: Combined analysis at physiological and molecular levels

Qian Wang,Xiangfeng Yao,Nan Jiang,Juan Zhang,Guanyong Liu,Xianxu Li,Can Wang,Zhongkang Yang,Jinhua Wang,Lusheng Zhu,Jun Wang

Butyl benzyl phthalate (BBP), a typical phthalate plasticizer, is frequently detected in aquatic environments, but its possible effects on fish liver are unknown. In this study, adult zebrafish were exposed to 5–500 μg/L BBP and cultured for 28 days. The toxicity mechanism of environmentally relevant concentrations of BBP in the liver was explored using integrated biomarker response (IBR), molecular docking, and histopathological analysis, based on the tests of oxidative stress, apoptosis, and tissue damage, respectively. The results revealed that exposure to 500 μg/L BBP caused lipid peroxidation and DNA damage and induced inflammatory responses in the liver and intestinal tissues. The accumulation of reactive oxygen species (ROS) is the primary manifestation of BBP toxicity and is accompanied by changes in the activities of antioxidant and detoxification enzymes. Notably, the pro-apoptotic genes ( p53 and caspase-3 ) were still significantly upregulated in the 50 μg/L and 500 μg/L treatment groups on day 28. Moreover, BBP interfered with apoptosis by forming a stable complex with apoptosis proteins (P53 and Caspase-3). Our findings are helpful for understanding the toxicity mechanisms of BBP, which could further promote the assessment of the potential environmental risks of BBP.

CAS / MDL: 85-68-7
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SCIENCE OF THE TOTAL ENVIRONMENT · 2023 · IF 9.8

Multi-walled carbon nanotubes enhance the toxicity effects of dibutyl phthalate on early life stages of zebrafish (Danio rerio): Research in physiological, biochemical and molecular aspects

Haiyue Chen,Yuexing Zhao,Tingting Zhao,Yanhong Li,Bo Ren,Hanlin Liang,Hongwu Liang

Phthalate esters (PAEs) are widely used as plasticizers. PAEs are ubiquitous in natural water bodies, with dibutyl phthalate (DBP) being one of the most common PAEs. DBP is prone to leaching or migration into the environment, posing serious health and environmental risks. Carbon nanotubes (CNTs) have been widely used in various fields with the rapid development of nanotechnology. CNTs could alter the environmental behavior and toxicity of co-existing pollutants. CNTs have been shown to rapidly adsorb PEAs. However, current knowledge about the effects of CNTs on DBP toxicity is limited. Here we show that the toxic effects of single and combined exposure to DBP (0.1, 0.5, 1.0 mg/L) and different CNTs (MWCNTs/MWCNTs-COOH, 0.5 mg/L) on the early growth stage of zebrafish. The results suggested that a significant increase in heart rate and heart malformation rate was observed after co-exposure of DBP and MWCNTs/MWCNTs-COOH ( p  < 0.05). Furthermore, combined exposure increased antioxidant enzyme activity during early developmental stages in zebrafish ( p  < 0.05). The qRT-PCR results revealed that DBP and MWCNTs/MWCNTs-COOH co-exposure significantly interfered with the expression of genes related to oxidative stress, energy metabolism, development of cardiac function, and apoptosis ( p  < 0.05). In addition, for oxidative stress and cardiotoxicity, MWCNTs/MWCNTs-COOH aggravated the toxic effects of 0.5 mg/L DBP on embryos/larvae. The metabolomics results showed that co-exposure mitigated the disturbance of amino acid metabolism mediated by single DBP exposure. In general, MWCNTs/MWCNTs-COOH increased the impact of DBP in the early developmental stages of zebrafish. This study provides new insights into the toxicology of early developmental stages of aquatic organisms exposed to co-exist pollutants of DBP and CNTs.

CAS / MDL: 175606-05-0
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SCIENCE OF THE TOTAL ENVIRONMENT · 2023 · IF 9.8

Individual and binary exposure of embryonic zebrafish (Danio rerio) to single-walled and multi-walled carbon nanotubes in the absence and presence of dissolved organic matter

Xibo Lu,Zhuang Wang

The available toxicological information was inadequate to assess the potential ecological risk of a mixture of different nanostructured carbon nanotubes (CNTs) to aquatic organisms, especially for the co-existence of mixed CNTs with dissolved organic matter (DOM). Herein, we investigated individual and binary exposure of zebrafish ( Danio rerio ) embryos to single-walled (SWCNTs) and multi-walled carbon nanotubes (MWCNTs) in the absence and presence of DOM. Results indicated that embryonic chorions were more resistant to mixed-type CNTs than to single-type CNTs, yet the addition of DOM decreased this resistance. The mixed-type CNTs increased the antioxidant capacity of zebrafish embryos by increasing superoxide dismutase activity in comparison to the single-type CNTs. Furthermore, the mixed-type CNTs caused oxidative damage to the zebrafish embryos, characterized by an increase in malondialdehyde level. Nevertheless, the activation of the antioxidant defense system was modulated by the presence of DOM. Transcriptome sequencing analysis showed that the number of unique genes (UGs) and differentially expressed genes (DEGs) between the mixed-type CNTs and control groups was significantly enhanced compared to the single-type CNTs. DOM increased the number of UGs and up-regulated DEGs, but decreased the number of down-regulated DEGs. GO classification analysis revealed that the mixed-type CNTs mainly altered the cellular component process of single-type CNTs to induce joint effects. DOM generally enhanced the GO enrichment of DEGs in D. rerio embryos exposed to the mixed-type CNTs during the biological process. KEGG pathway enrichment analysis for the mixed-type CNTs showed enrichment of DEGs encoding ether lipid metabolism, glycerophospholipid metabolism, glycerolipid metabolism, citrate cycle, and biosynthesis of nucleotide sugars. However, DOM allowed more specific KEGG pathways towards the mixed-type CNTs to be identified. Despite the mixed-type CNTs exhibiting differential expression of functional genes compared to the control and single-type CNTs, DOM could regulate the expression of these functional genes associated with oxidative stress response, carbohydrate metabolism, endoplasmic reticulum stress, neuroendocrine, osmotic stress, and DNA damage and repair. Our study thus paves a solid way for exploring the molecular mechanism of aquatic toxicity of multiple nanomaterials under field-relevant conditions.

CAS / MDL: 308068-56-6 1119-94-4
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