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CHEMOSPHERE · 2019 · IF 5.108

Predicting the survival of zebrafish larvae exposed to fluctuating pulses of lead and cadmium

Min Chen,Yongfei Gao,Xiaoxue Bian,Jianfeng Feng,Weiqi Ma,Lin Zhu

Aquatic organisms are often exposed to time-varied concentrations of contaminants due to pulsed inputs in natural water. Traditional toxicology experiments are usually carried out in a constant exposure pattern, which is inconsistent with the actual environment. In this study, a refined toxicokinetic-toxicodynamic (TK-TD) model was used to study the toxic effects of Pb and Cd on zebrafish larvae under three pulse exposures with 2, 4, and 6 h, respectively. The parameter sensitivity analysis showed that J M, max had the greatest impact on the output of the model. Cd or Pb pulse exposure resulted in less death than constant exposure at the same time-weighted average (TWA) concentrations. Survival fraction in larvae under 6 h interval between two pulses of Pb or Cd was larger than that under 2 h and 4 h interval. Toxicity under constant exposure of Cd or Pb was greater than that under 2, 4, and 6 h interval pulse exposure because the cumulative Cd or Pb concentration in the body under constant exposure was greater than that under pulse exposure. The results also showed that the stochastic death (SD) model was more suitable than the individual tolerance (IT) model for predicting the survival fraction of larvae under pulse exposure to Pb and Cd, which was indicated by higher R 2 (0.670–0.940) in SD model than that (0.588–0.861) in IT model. Our model provides approaches for laboratory toxicity testing and modeling approaches for addressing the toxicity of heavy metal pulsed exposure.

CAS / MDL: 7631-99-4
研究领域: 生态毒理学 · 环境科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Jove-Journal of Visualized Experiments · 2021 · IF 1.355

Using Alizarin Red Staining to Detect Chemically Induced Bone Loss in Zebrafish Larvae

Jie Ding,Rui Yan,Luna Wang,Qianlei Yang,Xiaoyun Zhang,Nan Jing,Yuanjie Wei,Hengdong Zhang,Yan An

Chemically induced bone loss due to lead (Pb) exposure could trigger an array of adverse impacts on both human and animal skeletal systems. However, the specific effects and mechanisms in zebrafish remain unclear. Alizarin red has a high affinity for calcium ions and can help visualize the bone and illustrate skeletal mineral mass. In this study, we aimed to detect lead acetate (PbAc)-induced bone loss in zebrafish larvae by using alizarin red staining. Zebrafish embryos were treated with a series of PbAc concentrations (0, 5, 10, 20 mg/L) between 2 and 120 h post fertilization. Whole-mount skeletal staining was conducted on larvae at 9 days post fertilization, and the total stained area was quantified using ImageJ software. The results indicated that the mineralized tissues were stained in red, and the stained area decreased significantly in the PbAc-exposure group, with a dose-dependent change in bone mineralization. This paper presents a staining protocol for investigating skeletal changes in PbAc-induced bone defects. The method can also be used in zebrafish larvae for the detection of bone loss induced by other chemicals.

研究领域: 毒理学 · 发育生物学 · 环境科学
✓ 已验证 DOI 高影响因子
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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
研究领域: 水生毒理学 · 药理学 · 环境科学
✓ 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

Polystyrene microplastics alter the toxicity of 6PPD to zebrafish (Danio rerio) larvae

Yuexing Zhao,Weitao Liu,Jianfeng Feng,Ning Gao,Jinzheng Liu,Ruiying Shi,Aurang Zeb,Jianling Wang,Qi Wang,Chuan Yin,Xinwei Shi,Xiang Li,Yichen Ge

Tire wear particles (TWPs) are a significant source of microplastics (MPs) and N -(1,3-dimethylbutyl)- N ′-phenyl- p -phenylenediamine (6PPD) in aquatic environments. However, the combined toxicity of MPs and 6PPD to aquatic organisms remains unclear. Here, we investigated the bioaccumulation of 6PPD, developmental toxicity, oxidative stress, and metabolic alterations in zebrafish larvae following single and combined exposure to polystyrene MPs (PSMPs) and 6PPD. Our results indicated that co-exposure to PSMPs and 6PPD induced synergistic toxicity in zebrafish larvae, significantly elevating levels of reactive oxygen species (ROS) and malondialdehyde (MDA), along with enhancing antioxidant enzyme activities. PSMPs did not influence the bioaccumulation of 6PPD, but increased the concentration of 6PPD quinone (6PPD-Q) in zebrafish larvae. PSMPs and 6PPD altered the metabolomic profiles of zebrafish larvae, affecting organic acids and their derivatives, amino acids and carbohydrates. The primary distinctions between single and combined exposures were observed in organic acids (citric acid and 9-Octadecenoic acid), sugars (D-Allose, D-Arabinose, and d-Mannose), and cholesterol. These findings imply PSMPs alter the toxicity of 6PPD to zebrafish larvae, providing valuable data for assessing the potential risks of single and combined pollution of MPs and 6PPD to aquatic creatures.

CAS / MDL: 793-24-8
研究领域: 环境毒理学 · 水生生物学 · 分子生态毒理学 · 代谢组学 · 污染物相互作用
✓ 已验证 产品关联 DOI PubMed 高影响因子
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PLoS One · 2016 ·Vol. 11 ·期 5 ·e0155762 · IF 3.057

The Effects of Disturbance on Hypothalamus-Pituitary-Thyroid (HPT) Axis in Zebrafish Larvae after Exposure to DEHP

Pan-Pan Jia,Yan-Bo Ma,Chun-Jiao Lu,Zakaria Mirza,Wei Zhang,Yong-Fang Jia,Wei-Guo Li,De-Sheng Pei

Di-(2-ethylhexyl) phthalate (DEHP) has the potential to disrupt the thyroid endocrine system, but the underlying mechanism is unknown. In this study, zebrafish ( Danio rerio ) embryos were exposed to different concentrations of DEHP (0, 40, 100, 200, 400 μg/L) from 2 to 168 hours post fertilization (hpf). Thyroid hormones (THs) levels and transcriptional profiling of key genes related to hypothalamus-pituitary-thyroid (HPT) axis were examined. The result of whole-body thyroxine (T4) and triiodothyronine (T3) indicated that the thyroid hormone homeostasis was disrupted by DEHP in the zebrafish larvae. After exposure to DEHP, the mRNA expressions of thyroid stimulating hormone ( tshβ ) and corticotrophin releasing hormone ( crh ) genes were increased in a concentration dependent manner, respectively. The expression level of genes involved in thyroid development ( nkx2 . 1 and pax8 ) and thyroid synthesis (sodium/iodide symporter, nis , thyroglobulin, tg ) were also measured. The transcripts of nkx2 . 1 and tg were significantly increased after DEHP exposure, while those of nis and pax8 had no significant change. Down-regulation of uridinediphosphate-glucuronosyl-transferase ( ugt1ab) and up-regulation of thyronine deiodinase ( dio2) might change the THs levels. In addition, the transcript of transthyretin ( ttr ) was up-regulated, while the mRNA levels of thyroid hormone receptors ( trα and trβ ) remained unchanged. All the results demonstrated that exposure to DEHP altered the whole-body thyroid hormones in the zebrafish larvae and changed the expression profiling of key genes related to HPT axis, proving that DEHP induced the thyroid endocrine toxicity and potentially affected the synthesis, regulation and action of thyroid hormones.

CAS / MDL: 886-86-2 582-33-2
研究领域: 环境科学 · 毒理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SCIENCE OF THE TOTAL ENVIRONMENT · 2020 · IF 6.551

Differential responses of larval zebrafish to the fungicide propamocarb: Endpoints at development, locomotor behavior and oxidative stress

Xin Liu,Rui Zhang,Yuanxiang Jin

The fungicide propamocarb (PM) is widely used to protect cucumbers, tomatoes and other plants from pathogens. According to previous studies, PM could be detected in the aquatic system in some area. However, the toxic effects of PM on zebrafish received very limited attention. In this study, we examined the toxic effects of various concentration of PM on the endpoints of development, locomotor behavior and oxidative stress in larval zebrafish. It was observed that PM exposure delayed embryonic development, inhibited hatchability at 60 and 72 h postfertilization and increased heart rate. After PM exposure, the larval zebrafish showed abnormal free swimming behavior and the swimming behavior in response to light-dark transition, indicating that PM had the potential to induce neurotoxicity. Moreover, PM exposure also affected the enzymatic activity of acetylcholinesterase and dopamine and the transcriptional level of genes related to neurotoxicity. In addition, PM exposure not only affects catalase (CAT), glutathione peroxidase (GPX), and glutathione S-transferase (GST) activity but also affects the transcription level of various genes. We believed that PM induced oxidative stress was also a possible reason to cause neurotoxicity in larval zebrafish. In summary, our results suggested that PM could disturb the endpoints at development, locomotor behavior and oxidative stress in larval zebrafish.

研究领域: 环境毒理学 · 水生生物学 · 神经科学
✓ 已验证 DOI PubMed 高影响因子
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AQUACULTURE NUTRITION · 2024 ·Vol. 2024 ·期 1 ·8368883 · IF 3

Dietary Oryzanol (Ory) Improved the Survival and Growth of Large Yellow Croaker (Larimichthys crocea) Larvae via Promoting Activities of Digestive Enzymes, Antioxidant Capacity, and Lipid Metabolism

Wenxuan Xu,Yuntao Wang,Jianmin Zhang,Jiahui Liu,Yongtao Liu,Wenxing Huang,Chuanwei Yao,Kangsen Mai,Qinghui Ai

A feeding study lasting 30 days was carried out to determine the effects of dietary Oryzanol (Ory) on the survival, growth, antioxidant capacity, peptic enzymes, as well as lipid metabolism of Larimichthys crocea larvae (11.87 ± 0.59 mg) using four different Ory concentrations in microfeed formulations (0, 20, 40, and 80 mg/kg), all preserving isolipidic (18.25% crude lipid) and isonitrogenous (52.08% crude protein) conditions. Results revealed that larvae given 40 and 80 mg/kg Ory revealed markedly higher survival rates; in particular, the 80 mg/kg Ory larvae exhibited a considerably higher specific growth rate than the control. Furthermore, the 80 mg/kg dietary Ory resulted in increased peptic enzyme activity, indicating heightened digestive capabilities of larvae. Meanwhile, Ory supplementation at 20, 40, and 80 mg/kg also increased antioxidant enzyme activities and reduced malondialdehyde levels, indicating an enhanced antioxidant capacity. Moreover, the incorporation of 20 and 40 mg/kg Ory demonstrated efficacy in enhancing the lipid metabolism of the larvae. This was evident in the reduction of triglyceride and total cholesterol levels in the larval visceral mass, attributed to the downregulation of genes that participate in lipid synthesis, and the upregulation of genes associated with lipid catabolism. Overall, the study suggests that the addition of Ory (ranging from 40 to 80 mg/kg) significantly improves both survival and developmental aspects, possibly mediated by enhanced digestion and antioxidative effects, alongside the induction of lipid metabolism in Larimichthys crocea larvae.

CAS / MDL: 11042-64-1 469-36-3
研究领域: 水产养殖学 · 营养学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ENVIRONMENTAL SCIENCE & TECHNOLOGY · 2025 · IF 11.3

Opposing Visual Impairments Induced by Structurally Similar Organophosphate Flame Retardants TPHP and CDP in Zebrafish Larvae

Yiqun Song,Ting Xu,Hongchang Zhang,Shuangqing Hu,Sheng Wei,Miao Cao,Huan Wang,Daqiang Yin

Vision is the primary sensory function for most animals and is also a sensitive toxic target of environmental pollutants. A new class of organophosphate flame retardants (OPFRs) termed emerging OPFRs (eOPFRs) with limited toxicological information is rapidly developed into the substitutes of traditional OPFRs. In this study, we investigated the visual toxicity of triphenyl phosphate (TPHP, one traditional OPFR) and cresyl diphenyl phosphate (CDP, one emerging OPFR) on zebrafish larvae at environmentally relevant concentrations (3 and 30 nM). After 5 days of exposure, an opposite toxicity was found between the two OPFRs, manifested in the light perception and the gene expressions of visual opsins. CDP caused a weak reaction to light and overall inhibition of opsin expression (0.7- to 0.8-fold) in the larvae, while TPHP tended to stimulate these events (1.2- to 2.4-fold). Besides, we identified a key transcription factor, tbx2a, that was significantly disrupted in both OPFRs’ exposure. The differing ways in which both OPFRs bind to Tbx2a may be the reason behind their opposite effects. These findings provided new clues for the toxicological mechanisms of OPFRs and revisited the question regarding safe substitutes for those emerging contaminants.

CAS / MDL: 115-86-6 26444-49-5
研究领域: 环境毒理学 · 发育生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF HAZARDOUS MATERIALS · 2020 · IF 9.038

Predicting copper toxicity in zebrafish larvae under complex water chemistry conditions by using a toxicokinetic–toxicodynamic model

Yongfei Gao,Jianfeng Feng,Jingxue Zhu,Lin Zhu

Multiple water chemistry parameters influence metal toxicity in natural waters and accurate quantification of those influences may accelerate the development of site-specific water quality criteria (WQC) and further execute metal risk assessment for better protection of aquatic biota. Here, we investigated the effects of water chemistry parameters on copper (Cu) toxicity of larval zebrafish ( Danio rerio ) and then incorporated the effects of key parameters in a Toxicokinetic and Toxicodynamic (TK-TD) model. Further, the proposed TK-TD model was used to predict Cu toxicity in laboratory artificial waters as well as natural water samples. The predictive performance of the TK-TD model was evaluated in comparison to the biotic ligand model (BLM). The results showed that increasing Ca, Mg, pH, and fulvic acid (FA) levels significantly mitigated Cu toxicity in larvae, while K and Na levels had no significant effect on Cu toxicity. A predictive TK-TD model based on these data described 91 % of Cu accumulation and 87 % of survival of larvae exposed to Cu under 0, 2.5, 5, 10 mg/L FA. Compared with BLM, TK-TD model predicted better Cu accumulation and toxicity for an independent dataset in low DOC concentration (<10.95 mg L −1 ) of 9 sites in Haihe river (Tianjin, China) media during 96 h exposure. The BLM under-predicted the acute Cu toxicity to larvae when compared with observed values. In high DOC concentration (13.12–17.78 mg L −1 ) among three field sites, BLM and TK-TD model both under-predicted the acute Cu toxicity to larvae when compared with observed values. Our research provides a TK-TD approach for predicting Cu toxicity under complex water chemistry conditions and deriving Cu-WQC in different scenarios where there exist limits for using the BLM.

研究领域: 环境科学 · 毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Environmental Sciences · 2022 · IF 6.796

Alleviative effects of a novel strain Bacillus coagulans XY2 on copper-induced toxicity in zebrafish larvae

Fang Ai,Xuedi Huang,Yalan Wu,Chen Ji,Yufang Gao,Ting Yu,Fujie Yan

Copper (Cu) is a kind of micronutrient element that is essential for human metabolism. However, it is also considered as an environmental pollutant which is toxic to organisms at a high concentration level. Probiotics , regarded as beneficial microorganisms for promoting human health, have functions of antioxidant capacity, immune-enhancing properties, intestinal barrier protection and regulation. Several studies have reported that probiotics show positive effects on alleviating and intervening heavy metals toxicity. However, evidence for relieving copper-induced toxicity by probiotics is still limited. In this study, we firstly conducted a zebrafish larvae model to screen out microorganisms which are helpful for CuSO 4 toxicity resistance and one novel strain named as Bacillus coagulans XY2 was discovered with the best protective activity. B. coagulans XY2 significantly reduced the mortality of zebrafish larvae exposed to 10 µmol/L CuSO 4 for 96 hr, as well as alleviated the neutrophils infiltration in the larvae lateral line under a 2 hr exposure. B. coagulans XY2 exhibited a high in vitro antioxidant activity and against CuSO 4 -induced oxidative stress in zebrafish larvae by up-regulating sod1, gstp1 and cat gene transcriptional levels and relevant enzymatic activities. CuSO 4 stimulated the inflammation process resulting in obvious increases of gene il-1β and il-10 transcription, which were suppressed by B. coagulans XY2 intervention. Overall, our results underline the bio-function of B. coagulans XY2 on protecting zebrafish larvae from copper toxicity, suggesting the potential application values of probiotics in copper toxicity alleviation on human and the environment.

研究领域: 环境毒理学 · 微生物学 · 水生生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2022 · IF 7.129

Ferroptosis is partially responsible for dexamethasone-induced T cell ablation, but not osteoporosis in larval zebrafish

Wenyu Miao,Lingling He,Yong Zhang,Xiaoyu Zhu,Yangming Jiang,Pengpeng Liu,Tao Zhang,Chunqi Li

Glucocorticoids (GCs) have been widely detected in the aquatic system. However, the hazardous effects of GCs on aquatic organisms were underestimated, and the mechanisms of GCs-induced toxic effects in fish were largely unknown. The zebrafish larvae at 3 dpf were exposed to dexamethasone (DEX) for 48 h, and the toxic effects and the underlying mechanisms were investigated in the current study. The T cells were ablated in zebrafish larvae after being treated with 1, 3, 10, 30 and 100 μM of DEX for 48 h. In addition, osteoporosis was induced and the regeneration of the caudal fin was inhibited, by 48 h-exposure to 10, 30 and 100 μM of DEX. The transcriptomic analysis, biochemical parameters and gene expression profiles revealed that ferroptosis possibly contributed to the DEX-induced toxic effects in zebrafish larvae. Finally, Fer-1 treatment partially attenuated the DEX-induced T cell ablation, but not osteoporosis in zebrafish larvae. Taken together, the current study proved the toxic effects of DEX on zebrafish larvae, and elucidated that ferroptosis was involved in DEX-induced toxicity, providing strong evidence for the toxic effects of GCs on aquatic organisms.

研究领域: 水生毒理学 · 免疫学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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CHEMISTRY OF MATERIALS · 2020 · IF 9.567

Multicenter-Emitting Carbon Dots: Color Tunable Fluorescence and Dynamics Monitoring Oxidative Stress In Vivo

Yi Wang,Ge Guo,Jialin Gao,Zhibin Li,Xueer Yin,Changqing Zhu,Yunsheng Xia

To date, dynamics monitoring oxidative stress on time resolution in vivo has not been achieved due to the limitation of probes, causing the difficulty to comprehensively understand its biological behaviors and functions. Herein, we propose a novel probe, namely highly bright and color tunable “multicenter-emitting” carbon dots (C-dots), for dynamics monitoring oxidative stress in vivo. Combined with experiments and theoretical calculations, we reveal that each C-dot contains multiple conjugated polyaromatic units on their surfaces, which act as fluorescent emitting centers and response sites of hypochlorous acid (HClO) to achieve an instantaneously color-change readout (107 nm, from yellow-green to blue). Accordingly, the proposed C-dots enable the observation of HClO burst and dynamics evolution at fresh wounds of zebrafish larvae. Such a burst occurs only at 1–5 s after cutting, which is an unprecedented thought regarding oxidative stress dynamics. Furthermore, the present study indicates that HClO molecules are principally generated in situ rather than migration.

研究领域: 化学 · 材料科学 · 生物学 · 分析化学
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