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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2023 · IF 6.8

Exposure to Butylparaben Induces Craniofacial Bone Developmental Toxicity in Zebrafish (Danio rerio) Embryos

Zekun Li,Kun Jia,Xiaomei Chen,Jun Guo,Zhiguo Zheng,Weihua Chen,Yuan Peng,Yuhao Yang,Huiqiang Lu,Jian Yang

Butylparaben (BuP) is a common antibacterial preservative utilized extensively in food, medical supplies, cosmetics, and personal care products. The current study reports the use of Zebrafish ( Danio rerio ) embryos to investigate potential developmental toxicity caused by exposure to BuP. The development of Neural crest cells (NCCs) is highly active during gastrulation in Zebrafish embryos. Thus, we utilized 0.5 mg/L, 0.75 mg/L, and 1 mg/L BuP solutions, respectively, in accordance with the international safety standard dosage. We observed severe craniofacial cartilage deformities, periocular edema, cardiac dysplasia, and delayed otolith development in the Zebrafish larvae 5 days after exposure. The oxidative stress response was significantly enhanced. In addition, the biochemical analysis revealed that the activities of catalase (CAT) and superoxide dismutase (SOD) were significantly reduced relative to the control group, whereas the concentration of malondialdehyde (MDA) was significantly elevated. Furthermore, ALP activity, a marker of osteoblast activity, was also reduced. Moreover, the RT-qPCR results indicated that the expression of chondrocyte marker genes sox9a, sox9b, and col2a1a was down-regulated. In addition, the morphology of maxillofacial chondrocytes was altered in Zebrafish larvae, and the proliferation of cranial NCCs was inhibited. Accordingly, our findings indicate that strong oxidative stress induced by BuP inhibits the proliferation of NCCs in larval Zebrafish, leading to craniofacial deformities.

CAS / MDL: 130-22-3 33864-99-2
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FISH & SHELLFISH IMMUNOLOGY · 2019 · IF 3.298

The hepatoprotective effects of Salvia plebeia R. Br. extract in zebrafish (Danio rerio)

Guanghua Xiong,Yunyun Deng,Zigang Cao,Xinjun Liao,Jun'e Zhang,Huiqiang Lu

Salvia plebeia R. Br. is a traditional Chinese medicinal herb that has been widely used for the treatment of many inflammatory diseases such as hepatitis. However, the underlying molecular mechanism about the hepatoprotective effects of S. plebeia remains largely unknown. Here, we investigated the antioxidant activities and anti-inflammatory effects of ethanol extracts of S. plebeia (SPEE) in the zebrafish model. Firstly, we determined the chemical compositions of SPEE and identified three major constituents by using GC-MS analysis. After that, SPEE exhibited significantly antioxidant properties in the LPS-induced zebrafish embryos, and the enzyme activities of ROS, CAT and SOD were obviously inhibited in a dose-dependent manner. Secondly, SPEE greatly reduced fat vacuoles (HE staining), lipid accumulation (Oil O staining) and hepatocyte fibrosis (Gemori staining) in the thioacetamide (TAA)-induced hepatocyte injury of adult zebrafish. Meanwhile, the NO contents and lipid metabolism-related genes were substantially down-regulated after SPEE exposure. Thirdly, we used RNA-Seq analysis to identify the differentially expressed genes (DEGs) after SPEE exposure in adult zebrafish liver. The results showed that 1289 DEGs including 558 up-regulated and 731 down-regulated were identified between the TAA + SPEE and TAA groups. KEGG pathway and GO functional analysis revealed that steroid biosynthesis , oxidation-reduction and innate immunity were significantly enriched. Mechanistically, SPEE can considerably reduce the cell apoptosis of hepatocytes and promote the translocation of Nrf2 protein from the nucleus to the cytoplasm in TAA-induced zebrafish. Moreover, SPEE can modulate various inflammatory cytokines and immune genes both in the control and H 2 O 2 -stimulated conditions. The pro-inflammatory cytokines such as IL-1β and TNF-α was markedly up-regulated but the anti-inflammatory cytokines such as TGF-β was greatly down-regulated after SPEE treatment. In addition, some key genes in the TLR signaling were also activated in the H 2 O 2 -stimulated conditions. In summary, our results suggested that SPEE had an important role in the antioxidant and anti-inflammatory effects in zebrafish in the near future. Some of the components identified in this study may be served as potential sources of new hepatoprotective compounds for the treatment of inflammatory diseases.

CAS / MDL: 7722-84-1
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ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH · 2018 ·Vol. 25 ·期 24 ·23799-23808 · IF 2.8

Impacts of isopyrazam exposure on the development of early-life zebrafish (Danio rerio)

Yao Hongzhou,Xu Xiao,Zhou Ying,Xu Chao

Isopyrazam (IPZ) is a broad spectrum succinate dehydrogenase inhibitor fungicide. Little is known about its potential ecological risks of aquatic organisms recently. The present study examined the embryonic development effects of zebrafish exposed to IPZ under static condition using a fish embryo toxicity test. The lowest observed effect concentration of IPZ was 0.025 mg/L in 4-day exposure. Developmental abnormalities, including edema, small head deformity, body deformation and decreased pigmentation, and mortality were observed in zebrafish embryos of 0.05 mg/L and higher concentrations, which shown concentration dependency. The heart rate of zebrafish was disrupted by IPZ. Moreover, enzyme and gene experiments shown that IPZ exposure caused oxidative stress of zebrafish. Furthermore, it induced a decrease of succinate dehydrogenase (SDH) enzyme activity and gene transcription level in zebrafish larvae. It can be speculated that IPZ may have a lethal effect on zebrafish, which is accompanied by decreased SDH activity, oxidative stress, and abnormality. These results provide toxicological data about the IPZ on aquatic non-target organisms, which could be useful for further understanding potential environmental risks.

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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2016 · IF 3.13

Prometryn and humic acid induce Cytochrome P450 1A expression in Danio rerio (zebrafish)

Qian Zhao,Feng Shi,Lin Zhu

Humic acid (HA) is a major component of dissolved organic matter , is ubiquitous in the aquatic environment and influences the biological toxicity of organic pollutants. In this study, we investigated the cytochrome P450 1A (CYP 1A) mRNA expression and ethoxyresorufin- O -deethylase (EROD) activity in the gills and liver of zebrafish following exposure to the s -triazine herbicide prometryn with or without HA present. Prometryn induced both CYP 1A mRNA expression and EROD activity. The CYP 1A mRNA expression of zebrafish that were exposed to a combination of prometryn and HA was increased compared to those exposed to prometryn alone. A likely cause for CYP 1A induction is the impact of special components of HA, functioning as aryl hydrocarbon receptor (AHR) agonists. In combination with HA, these increase prometryn levels in tissues. Similar results for EROD activity were evident. In our time course study, CYP 1A mRNA expression reached maximum values during 24   h. This revealed CYP 1A mRNA transcription as a comparatively sensitive toxicity index. In a recovery experiment, we found a faster decrease of CYP 1A mRNA expression to control levels (CK) in gills compared to liver tissue. Following exposure to HA, CYP 1A mRNA expression in liver tissue displayed a faster decrease to CK levels. HA induced enhanced metabolic rates for prometryn. In contrast, recovery regularity of CYP 1A expression in gills was independent of the presence of HA. This result indicates different detoxification mechanisms for HA in liver and gills.

CAS / MDL: 7287-19-6
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ENVIRONMENTAL RESEARCH · 2025 · IF 7.7

ADB-FUBINACA-induced developmental toxicity, neurotoxicity, and cardiotoxicity in embryonic zebrafish (Danio rerio)

Yuanzhao Wu,Fengjun Fan,Lu Zhou,Yihang Shen,Anli Wang,Yazhou Qin,Jiye Wang,Weixuan Yao

As an emerging pollutant, the synthetic cannabinoid N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide (ADB-FUBINACA) is widely abused and frequently detected in metropolitan wastewater. However, its effect on aquatic organisms remains unexplored. In this study, embryonic and larval zebrafish were exposed to sublethal concentrations of ADB-FUBINACA to assess its toxic effects via behavioral, biochemical, and metabolomic analyses. The observed morphological defects included reduced heartbeat, shorter body length, spinal deformation, and pericardial edema. Transgenic zebrafish exhibited cardiac developmental defects and apoptosis, indicating that cardiotoxicity is associated with dysregulated gene expression. Impaired motor activity and disrupted neuronal development suggested neurotoxicity. Elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels indicate oxidative stress, whereas transcriptional changes in immune-related genes reflect a dysregulated inflammatory response. Metabolomic analyses revealed disruptions in pathways related to alanine, purine, and pyrimidine metabolism, and arginine biosynthesis, which correlated with oxidative damage, cardiotoxicity, and neurodevelopmental effects. In conclusion, ADB-FUBINACA induces developmental toxicity in zebrafish embryos via oxidative stress and metabolic disruption, highlighting the potential environmental risks posed by this emerging pollutant.

CAS / MDL: 886-86-2
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Biology-Basel · 2025 ·Vol. 14 ·期 10 ·1408 · IF 3.5

Toxicological Mechanism of the Size–Form Synergy of Nano-Copper Oxide in Danio rerio

Qi Liu,Xiaoxuan Li,Lixin Fang,Yanhui Wang,Fang Sun,Peng Liu

Simple SummaryThe widespread industrial use of copper oxide nanoparticles (CuO-NPs) has inevitably led to their release into aquatic ecosystems. However, the toxicological effects of CuO-NPs, that is, its biological toxicity, particularly its correlation with particle size and morphology, remains inadequately studied. This study employed zebrafish to evaluate the toxicity of CuO-NPs with varying particle sizes and morphologies. Organ-specific damage was observed in gills, livers, and intestines. Flake-shaped CuO-NPs (SC) exhibited greater toxicity than spherical particles, with smaller particle sizes showing increased toxicity. The primary mechanisms involved reduced tissue antioxidant capacity and diminished microbial α-diversity. Changes in the relative abundance of dominant taxonomic groups at phylum and genus levels contributed to multi-organ toxicity. These findings lay a foundation for the study of the toxicity mechanism of nanomaterials.CuO-NPs demonstrate significant potential across biomedical, environmental protection, and electronic technology domains. This widespread utilization inevitably leads to their discharge into aquatic ecosystems. Research on the biotoxicity of CuO-NPs constitutes a current scientific priority; however, toxicological impacts related to particle size and morphology remain inadequately documented. The zebrafish (Danio rerioRoloff, 1956) is employed as a model animal organism to assess acute and subchronic toxicity of differentially sized/shaped CuO-NPs. Organ-specific damage manifested in the gills, liver, and muscles. It was found that sheet-shaped CuO-NPs (SC) could induce the most severe histomorphological alterations. Among spherical CuO-NPs (SP), smaller particles exhibited higher toxicity (SC > 40 nm SP-S > 150–250 nm SP-L). Tissue antioxidant capacity followed the same decreasing trend. The three CuO-NPs in the present study reduced microbial alpha-diversity. Altered relative abundance of dominant taxa is observed at the phylum and genus levels. These results expand toxicological datasets for nanomaterial–vertebrate interactions and support environmental risk assessment for nano-pollutants in natural conditions.

CAS / MDL: 1317-38-0
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PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY · 2023 · IF 4.7

Enantioselective effects of paclobutrazol and its enantiomers on glycolipid metabolism in zebrafish (Danio rerio)

Dong Guo,Simin Chen,Weiguang Zhang,Jun Fan

Paclobutrazol is a plant growth inhibitor widely used in agricultural production. However, toxicology studies of paclobutrazol enantiomers towards aquatic organisms are limited. Herein, effects of paclobutrazol and its two enantiomers (2 R , 3 R ; 2 S , 3 S ) on glycolipid metabolism of zebrafish have been systemically explored at the concentration of 10 mg/L through biochemical analyses, LC-MS/MS, molecular dynamics simulation, and gene expression. In all treatments, the contents of glucose, citric acid and lactate significantly were increased while the glycogen and pyruvate contents were decreased, in which (2 R , 3 R )-paclobutrazol exhibited a greater effect than the (2 S , 3 S )-enantiomer ( P  < 0.05). Then, activities of hexokinase and lactate dehydrogenase in (2 R , 3 R )-paclobutrazol treatment were 0.74- and 1.18-fold higher than (2 S , 3 S )-enantiomer treatment, respectively ( P  < 0.001), and the results of molecular dynamics simulation revealed that the binding free energy of hexokinase 1 to (2 R , 3 R )-paclobutrazol was higher than that to the antipode. Moreover, lipids including triglycerides , total cholesterol , fatty acids, bile acids and glycerophospholipids in zebrafish were strikingly affected after paclobutrazol exposure. The (2 R , 3 R )-paclobutrazol-treated group showed the most obvious changes, indicating that it possessed much stronger disruption ability on the lipid metabolism of zebrafish. Furthermore, qRT-PCR analysis results revealed that (2 R , 3 R )-enantiomer significantly impacted expressions of glycolipid metabolism-related genes ( hk1 , g6pc , pck1 , pk , aco , cebpa , cyp51 , fasn and ppara ) in zebrafish than (2 S , 3 S )-enantiomer ( P  < 0.05). Briefly, this study provides new evidences for the toxicity of paclobutrazol to aquatic organisms and the potential risk to human health at the chiral level.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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Geoscience Frontiers · 2022 · IF 7.483

Polystyrene nanoplastics aggravated ecotoxicological effects of polychlorinated biphenyls in on zebrafish (Danio rerio) embryos

Yizheng Li,Shulin Liu,Qiuping Wang,Yanling Zhang,Xikun Chen,Lei Yan,Muhammad Junaid,Jun Wang

In view of the accumulation of nanoplastics (NPs) in the food chain of environment and animals, and the good adsorption properties of nano-plastics to toxic substances, it is necessary to explore the influence of NPs in living organisms. In this study, single and joint toxicological effects of polystyrene nanoplastics (PS-NPs, size 80 nm) and polychlorinated biphenyls (PCBs), were explored in freshwater aquatic animal model zebrafish ( Danio rerio ). Our study found that exposure to single PS-NPs induced mild acute toxicity, albeit the combined exposure of PS-NPs and polychlorinated biphenyls aggravated the toxicity of PCBs in a dose-dependent manner. Results from gene expression profiling showed that NPs exposure could activate detoxification process, resulting in a slight up-regulation of antioxidant genes ( sod1 , gstp1 ), bone development genes ( bmp2 , bmp4 ) and cardiac gene ( tbx20 ); while PCBs suppressed the detoxification through down-regulation of these genes, and the addition of NPs will exacerbate the impact of PCBs on gene suppression. Importantly, the results of in vivo purification experiments found that NPs showed prolonged retention in liver, intestine and gills of zebrafish and they might have crossed biological barrier and accumulate in lipid-rich tissues and excretion does not appear as the significant pathway for their elimination. In conclusion, the toxic effects of polychlorinated biphenyls on chorionic protected embryos were not significant as zebrafish chorion plays an important role in resisting the invasion of pollutants; PCBs can seriously damage the bone and heart development of zebrafish, while the presence of NPs significantly enhanced the toxicity of PCBs in zebrafish, which is an alarming concern for growing NPs levels and ecological safety in aquatic environment.

CAS / MDL: 32598-13-3
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FISH & SHELLFISH IMMUNOLOGY · 2023 · IF 4.7

Alleviative effects of quercetin of Botrytis cinerea-induced toxicity in zebrafish (Danio rerio) larvae

Shengnan Shi,Ju Wang,Changhong Liu,Lei Zheng

Quercetin is a kind of flavonoid substance extensively existing in the plant, which has antioxidant, anti-inflammatory, and anti-apoptosis effects. It was reported that the higher concentration of spores present in the environment could cause abnormal development in zebrafish larvae. Therefore, this study set out to investigate whether quercetin could reduce the zebrafish larvae damage caused by Botrytis cinerea exposure as well as to examine the molecular basis for this action. The findings demonstrated that 50 μM quercetin improved the developmental dysplasia of zebrafish larvae induced by 10 2  CFU/mL Botrytis cinerea spore suspension, reduced abnormal apoptosis, enhanced antioxidant system, relieved inflammation, reshaped intestinal morphology and recovered intestinal motility . At the molecular level, quercetin decreased the transcriptional abundance of pro-apoptotic factors ( bax , p53 , caspase3 , and caspase9 ) and up-regulated the anti-apoptotic gene ( bcl-2 ) expression to reduce apoptosis. Moreover, quercetin enhanced the activities of downstream antioxidant enzymes (SOD and CAT) to clear excess ROS and MDA due to Botrytis cinerea exposure by up-regulating the expression of antioxidant genes ( nrf2 , ho-1 , sod , and cat ) in the Keap1-Nrf2 pathway. Additionally, quercetin inhibited the elevation of TNF-α by regulating the gene expression of key targets ( jak3 , pi3k , pdk1 , akt , and ikk2 ) and the content of major proteins NF-κB (P65) and IκB in the NF-κB pathway. In conclusion, this work enriched the contents of the biological research of Botrytis cinerea and provided a new direction for the drug development and targeted therapy of quercetin.

CAS / MDL: 117-39-5
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BULLETIN OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY · 2019 ·Vol. 103 ·期 2 ·267-273 · IF 1.65

A Near-infrared Persistent Luminescence Imaging Technique for Tracking Nanoparticles in Zebrafish (Danio rerio)

Wang Chengcheng,Zheng Shenghui,Zou Xiaoyan,Sun Xia,Zhang Hongwu

The development of nanotechnology has drawn increased attention to the risks of nanoparticles (NPs). In this work, the near-infrared persistent luminescence imaging technique was used to track the biodistribution of NPs in vivo in zebrafish. Zebrafish were used as a vertebrate animal model to show NPs distribution and the effects of exposure. ZnGa 2 O 4 :Cr (ZGOC) was chosen as the probe in this work. In continuous exposure experiments, the results showed more particles accumulated in the intestines than in the gills in both groups. In both the gills and abdomen, the NPs contents were greater in the ZGOC–NH 2 -treated groups than in the ZGOC groups, and the NPs caused damage to the gills and intestines. Removal exposure experiments indicated that ZGOC and ZGOC–NH 2 could be excreted from the body. The metabolism, excretion of NPs, the quantification and monitoring of NPs behavior in biological systems should be examined in further studies.

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ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH · 2016 ·Vol. 23 ·期 18 ·18832-18841 · IF 2.76

Acute toxicity and histopathological effects of naproxen in zebrafish (Danio rerio) early life stages

Li Qian,Wang Peipei,Chen Ling,Gao Hongwen,Wu Lingling

Zebrafish ( Danio rerio ) embryos and larvae were selected to investigate the potential risk and aquatic toxicity of a widely used pharmaceutical, naproxen. The acute toxicity of naproxen to embryos and larvae was measured, respectively. The histopathology was investigated in the liver of zebrafish larvae after 8-day embryo-larvae exposure to naproxen. The values of 96-h LC 50 were 115.2 mg/L for embryos and 147.6 mg/L for larvae, indicating that zebrafish embryos were more sensitive than larvae to naproxen exposure. Large suites of symptoms were induced in zebrafish ( D. rerio ) early life stages by different dosages of naproxen, including hatching inhibition, lower heart rate, and morphological abnormalities. The most sensitive sub-lethal effect caused by naproxen was pericardial edema, the 72-h EC 50 values of which for embryos and larvae were 98.3 and 149.0 mg/L, respectively. In addition, naproxen-treated zebrafish larvae exhibited histopathological liver damage, including swollen hepatocytes, vacuolar degeneration, and nuclei pycnosis. The results indicated that naproxen is a potential threat to aquatic organisms.

CAS / MDL: 50-00-0
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SCIENCE OF THE TOTAL ENVIRONMENT · 2024 · IF 8.2

Liver damage and lipid metabolic dysregulation in adult zebrafish (Danio rerio) induced by spirotetramat

Xunyue Liu,Haojie Zhu,Peng Liu,Junyao Ge,Qiong Rao,Wenze He,Jianqiang Sun

Spirotetramat, an insecticide derived from cycloketone and extensively utilized in agricultural production, has been reported to be toxic to an array of aquatic organisms. Previous studies have indicated that spirotetramat can cause toxicity such as impaired ovarian development and apoptosis in zebrafish, but its toxicological effects on lipid metabolism and liver health in zebrafish remain unclear. In this study, we explored the effects of spirotetramat exposure on zebrafish ( Danio rerio ) by examining key markers of lipid metabolism, alterations in gene expression related to this process, and histological characteristics of the liver. Spirotetramat significantly reduced the condition factor, triglycerides and low-density lipoprotein cholesterol levels at 2 mg/L. The expression of genes related to fatty acid synthesis ( acacb ), β-oxidation ( acox1 , pparda ) and pro-inflammatory cytokines ( tnf-α , il-1β ) was downregulated. However, the expression of genes related to lipid transport and uptake ( cd36 , ppara ) and output ( apob ) was upregulated. The activity of alanine aminotransferase was significantly inhibited. Histopathology results showed that spirotetramat exposure led to liver cell vacuolation and necrosis. In addition, molecular docking results of spirotetramat and lipid transport related protein ( ACC , ApoB ) in both zebrafish and human showed the binding energy of human proteins is lower than that for zebrafish, and that the number of hydrogen bonds formed was higher. It is speculated that spirotetramat may also pose a significant potential hazard to humans, potentially affecting human lipid metabolism and health. This study expunge shed light on the ecological toxicity of spirotetramat by showing how it disrupts lipid metabolism and causes tissue damage specifically in zebrafish liver, contributing to a deeper understanding of its harmful effects in aquatic environment.

CAS / MDL: 203313-25-1
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