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Effect of flupyradifurone on zebrafish embryonic development
2021
Zhong, Keyuan | Meng, Yunlong | Wu, Juan | Wei, You | Huang, Yong | Ma, Jinze | Lu, Huiqiang
Evaluation of the toxicity of pesticide residues on non-target organisms in the ecosystem is an important part of pesticide environmental risk assessment. Flupyradifurone is a new type of butenolide insecticide produced by Bayer, who claims it to be “low toxic” to non-target organisms in the environment. However, there is little evidence in the literature to show how flupyradifurone affects aquatic organism development. In the current study, zebrafish embryos were treated with 0.1, 0.15, and 0.2 mg/mL of flupyradifurone within 6.0–72 h past fertilization (hpf). We found that the half-lethal concentration (LC₅₀) of flupyradifurone for zebrafish embryos at 96 hpf was 0.21 mg/mL. Flupyradifurone decreases the heart rate, survival rate, and body length of zebrafish embryos. The flupyradifurone treatment also led to the failure of heart looping, and pericardial edema. Moreover, flupyradifurone increased the level of reactive oxygen species (ROS) and decreased the enzymatic catalysis of catalase (CAT) and superoxide dismutase (SOD). Alterations were induced in the transcription of apoptosis-related genes (bcl-2, bax, bax/bcl-2, p53 and caspase-9) and the heart development-related genes (gata4, myh6, nkx2.5, nppa, tbx2b, tbx5 and vmhc). In the current study, new evidences have been provided regarding the toxic effects of flupyradifurone and the risk of its residues in agricultural products and the environment.
اظهر المزيد [+] اقل [-]Arsenic exposure induces a bimodal toxicity response in zebrafish
2021
Coral, Jason A. | Heaps, Samuel | Glaholt, Stephen P. | Karty, Jonathan A. | Jacobson, Stephen C. | Shaw, Joseph R. | Bondesson, Maria
In toxicology, standard sigmoidal concentration-response curves are used to predict effects concentrations and set chemical regulations. However, current literature also establishes the existence of complex, bimodal concentration-response curves, as is the case for arsenic toxicity. This bimodal response has been observed at the molecular level, but not characterized at the whole organism level. This study investigated the effect of arsenic (sodium arsenite) on post-gastrulated zebrafish embryos and elucidated effects of bimodal concentration-responses on different phenotypic perturbations.Six hour post fertilized (hpf) zebrafish embryos were exposed to arsenic to 96 hpf. Hatching success, mortality, and morphometric endpoints were evaluated both in embryos with chorions and dechorionated embryos. Zebrafish embryos exhibited a bimodal response to arsenic exposure. Concentration-response curves for exposed embryos with intact chorions had an initial peak in mortality (88%) at 1.33 mM arsenic, followed by a decrease in toxicity (~20% mortality) at 1.75 mM, and subsequently peaked to 100% mortality at higher concentrations. To account for the bimodal response, two distinct concentration-response curves were generated with estimated LC10 values (and 95% CI) of 0.462 (0.415, 0.508) mM and 1.69 (1.58, 1.78) mM for the ‘low concentration’ and ‘high concentration’ peaks, respectively. Other phenotypic analyses, including embryo length, yolk and pericardial edema all produced similar concentration-response patterns. Tests with dechorionated embryos also resulted in a bimodal toxicity response but with lower LC10 values of 0.170 (0.120, 0.220) mM and 0.800 (0.60, 0842) mM, respectively. Similarities in bimodal concentration-responses between with-chorion and dechorionated embryos indicate that the observed effect was not caused by the chorion limiting arsenic availability, thus lending support to other studies such as those that hypothesized a conserved bimodal mechanism of arsenic interference with nuclear receptor activation.
اظهر المزيد [+] اقل [-]A multi-omics approach reveals molecular mechanisms by which phthalates induce cardiac defects in zebrafish (Danio rerio)
2020
Mu, Xiyan | Chen, Xiaofeng | Liu, Jia | Yuan, Lilai | Wang, Donghui | Qian, Le | Qian, Yu | Shen, Gongming | Huang, Ying | Li, Xuxing | Li, Yingren | Lin, Xiangming
The potential risks of phthalates affecting human and animal health as well as the environment are emerging as serious concerns worldwide. However, the mechanism by which phthalates induce developmental effects is under debate. Herein, we found that embryonic exposure of zebrafish to di-(2-ethylhexyl) phthalate (DEHP) and di-butyl phthalate (DBP) increased the rate of heart defects including abnormal heart rate and pericardial edema. Changes in the transcriptional profile demonstrated that genes involved in the development of the heart, such as tbx5b, nppa, ctnt, my17, cmlc1, were significantly altered by DEHP and DBP at 50 μg/L, which agreed with the abnormal cardiac outcomes. Methylated DNA immunoprecipitation sequencing (MeDIP-Seq) further showed that significant hypomethylation of nppa and ctnt was identified after DEHP and DBP exposure, which was consistent with the up-regulation of these genes. Notably, hypermethylation on the promoter region (<1 kb) of tbx5b was found after DEHP and DBP exposure, which might be responsible for its decrease in transcription. In conclusion, phthalates have the potential to induce cardiac birth defects, which might be associated with the transcriptional regulation of the involved developmental factors such as tbx5b. These findings would contribute to understand the molecular pathways that mediated the cardiac defects caused by phthalates.
اظهر المزيد [+] اقل [-]The lipid metabolism alteration of three spirocyclic tetramic acids on zebrafish (Danio rerio) embryos
2019
Zhang, Jie | Qian, Le | Teng, Miaomiao | Mu, Xiyan | Qi, Suzhen | Chen, Xiangguang | Zhou, Yimeng | Cheng, Yi | Pang, Sen | Li, Xuefeng | Wang, Chengju
Spirocyclic tetramic acids are widely used in controlling phytophagous mite species throughout the world. the data set is incomplete and provides insufficient evidence for drawing the same conclusion for fish. To fill the gap whether these acaricides alter lipid metabolism on vertebrates, zebrafish embryos exposed to a series concentration of pesticides, the developmental effects, enzyme activities and levels of gene expression were assessed, battery of biomarker utilized by the integrated biomarker response (IBRv2) model. The 96 h-LC₅₀ of spirodiclofen, spiromesifen and spirotetramat were 0.14, 0.12 and 5.94 mg/L, respectively. Yolk sac deformity, pericardial edema, spinal curvature and tail malformation were observed. Three spirocyclic acids were unfavouring the lipid accumulation of by inhibited the acetyl-CoA carboxylase (ACC), fatty acid synthesis (FAS), fatty acid binding proteins (FABP2) and lipoprotein lipase (LPL) activity. The total cholesterol (TCHO) level significantly decreased in the 0.072 mg/L spirodiclofen group and 0.015 and 0.030 mg/L in the spiromesifen groups. No expected change in spirotetramat group on the TCHO and triglycerides (TGs) levels for any of the treatments. The mRNA levels of the genes related to lipid metabolism also significantly altered. In both spirodiclofen and spiromesifen, ACC achieved the highest scores among a battery of biomarkers using integrated biomarker response (IBRv2). The results suggest that spiromesifen was the most toxic for embryos development and spirodiclofen was the most toxic for lipid metabolism in embryos. The 0.07 mg/L of spirodiclofen, 0.05 mg/L of spiromesifen and 2.00 mg/L would cause malformation on zebrafish embryos. This study will provide new insight that fatty acid metabolism may be a suitable biomarker for the spirocyclic tetramic acids in fish species.
اظهر المزيد [+] اقل [-]Cardio-respirometry disruption in zebrafish (Danio rerio) embryos exposed to hydraulic fracturing flowback and produced water
2017
Folkerts, Erik J. | Blewett, Tamzin A. | He, Yuhe | Goss, Greg G.
Hydraulic fracturing to extract oil and natural gas reserves is an increasing practice in many international energy sectors. Hydraulic fracturing flowback and produced water (FPW) is a hyper saline wastewater returned to the surface from a fractured well containing chemical species present in the initial fracturing fluid, geogenic contaminants, and potentially newly synthesized chemicals formed in the fracturing well environment. However, information on FPW toxicological mechanisms of action remain largely unknown. Both cardiotoxic and respirometric responses were explored in zebrafish (Danio rerio) embryos after either an acute sediment-free (FPW-SF) or raw/sediment containing (FPW-S) fraction exposure of 24 and 48 h at 2.5% and 5% dilutions. A 48 h exposure to either FPW fraction in 24–72 h post fertilization zebrafish embryos significantly increased occurrences of pericardial edema, yolk-sac edema, and tail/spine curvature. In contrast, larval heart rates significantly decreased after FPW fraction exposures. FPW-S, but not FPW-SF, at 2.5% doses significantly reduced embryonic respiration/metabolic rates (MO2), while for 5% FPW, both fractions reduced MO2. Expression of select cardiac genes were also significantly altered in each FPW exposure group, implicating a cardiovascular system compromise as the potential cause for reduced embryonic MO2. Collectively, these results support our hypothesis that organics are major contributors to cardiac and respiratory responses to FPW exposure in zebrafish embryos. Our study is the first to investigate cardiac and respiratory sub-lethal effects of FPW exposure, demonstrating that FPW effects extend beyond initial osmotic stressors and verifies the use of respirometry as a potential marker for FPW exposure.
اظهر المزيد [+] اقل [-]Developmental alterations, teratogenic effects, and oxidative disruption induced by ibuprofen, aluminum, and their binary mixture on Danio rerio
2021
Sánchez-Aceves, Livier M | Pérez-Alvarez, Itzayana | Gómez-Oliván, Leobardo Manuel | Islas-Flores, Hariz | Barceló, Damià
Several studies highlighted the ubiquitous presence of ibuprofen and aluminum in the aquatic environment around the world and demonstrated their potential to induce embryotoxic and teratogenic defects on aquatic species individually. Although studies that evaluate developmental alterations induced by mixtures of these pollutants are scarce; and, since environmental contamination presented in the form of a mixture of toxicants with different chemical properties and toxicity mechanisms capable of generating interactions; the objective of this study was to evaluate the developmental defects, teratogenic alterations, and oxidative stress induced by individual forms and the mixture of ibuprofen (IBU) and aluminum (Al) on zebrafish embryos. Oocytes exposed to environmentally relevant concentrations of IBU (0.1–20 μg L-1) and Al (0.01–8 mg L-1) and one binary mixture. The LC50 and EC50 were obtained to calculate the teratogenic index (TI). The IBU LC50, EC50, and TI were 8.06 μg L-1, 2.85 μg L-1 and 2.82. In contrast, Al LC50 was 5.0 mg L-1with an EC50 of 3.58 mg L-1 and TI of 1.39. The main alterations observed for individual compounds were hatching alterations, head malformation, skeletal deformities, hypopigmentation, pericardial edema, and heart rate impairment. The mixture also showed significant delays to embryonic development. Moreover, oxidative stress biomarkers of cellular oxidation and antioxidant defenses at 72 and 96 hpf significantly increased. Results show that environmentally relevant concentrations of ibuprofen (IBU), aluminum (Al), and their mixture promote a series of developmental defects, teratogenic effects, and oxidative disruption on D. rerio embryos, and the interaction of both substances altered the response. In conclusion, morphological and biochemical tests are suitable tools for assessing the health risk of aquatic wildlife by exposure to individual and mixed pollutants in freshwater bodies.
اظهر المزيد [+] اقل [-]Risk assessment of cardiotoxicity to zebrafish (Danio rerio) by environmental exposure to triclosan and its derivatives
2020
Wang, Danting | Zhang, Yuhuan | Li, Jieyi | Dahlgren, Randy A. | Wang, Xuedong | Huang, Haishan | Wang, Huili
Triclosan (TCS) and its two derivatives (2,4-dichlorophenol and 2,4,6-trichlorophenol) are priority pollutants that coexist in aquatic environments. Joint exposure of TCS, 2,4-dichlorophenol and 2,4,6-trichlorophenol, hereafter referred to as TCS-DT, contributes severe toxicity to aquatic organisms. There is currently a paucity of data regarding TCS-DT molecular toxicity, especially on cardiac diseases. We used zebrafish (Danio rerio) as a model organism, and evaluated the molecular-level cardiotoxicity induced by TCS-DT from embryonic to adult stages. TCS-DT exposure prominently led to phenotypic malformations, such as pericardial cysts, cardiac bleeding, increased SV-BA distance, decreased heart rate and reduced ejection fraction, as well as abnormal swimming behavior. Analyses of the GO and KEGG pathways revealed enrichment pathways related to cardiac development and screened for significantly down-regulated adrenaline signaling in cardiomyocytes. The cardiac marker genes (amhc, cmlc2, vmhc, and nkx2.5) were obtained through protein-protein interaction (PPI) networks, and expressed as down-regulation by WISH. After chronic exposure to TCS-DT from 30 to 90-dpf, both body mass and heart indexes prominently increased, showing myocardial hypertrophy, abnormal heart rate and histopathological injury. Heart tissue damage included disordered and ruptured myocardial fibers, broken and dissolved myofilaments, nuclear pyknosis, mitochondrial injury and inflammatory cell infiltration. Further, abnormal changes in a series of cardiac functions-related biomarkers, including superoxide dismutase, triglyceride, lactate dehydrogenase and creatinine kinase MB, provided evidence for cardiac pathological responses. These results highlight the molecular mechanisms involving TCS-DT induced cardiac toxicity, and provide theoretical data to guide prevention and treatment of pollutant-induced cardiac diseases.
اظهر المزيد [+] اقل [-]Exposure to diclofop-methyl induces cardiac developmental toxicity in zebrafish embryos
2020
Cao, Zigang | Huang, Yong | Xiao, Juhua | Cao, Hao | Peng, Yuyang | Chen, Zhiyong | Liu, Fasheng | Wang, Honglei | Liao, Xinjun | Lu, Huiqiang
Diclofop-methyl (DM) is one of the most widely used herbicides in agriculture production and has been frequently detected in both freshwater and environments, even agricultural products. However, the potential toxic effects of DM on organisms and the underlying mechanisms are still poorly understood. In this study, we utilized zebrafish to evaluate the toxicity of DM during the cardiovascular developmental process. Exposure of zebrafish embryos to 0.75, 1.0 and 1.25 mg/L DM induced cardiac defects, such as pericardial edema, slow heart rate and long SV-BA distance but the vascular development in zebrafish larvae was not influenced by DM treatment. The expression of cardiac-related genes were disordered and DM exposure initiated disordering cardiogenesis from the period of precardiac mesoderm formation. Moreover, the apoptosis and proliferation of cardiomyocytes were not influenced but the levels of oxidative stress were upregulated by DM exposure. Fullerenes and astaxanthin was able to rescue cardiac defects caused by DM via downregulating oxidative stress. Wnt signaling was downregulated after DM treatment and activation of Wnt signaling could rescue cardiac defects. Therefore, our results suggest that DM has the potential to induce cardiac developmental toxicity through upregulation of Wnt-Mediated (reactive oxygen species) ROS generation in zebrafish larvae.
اظهر المزيد [+] اقل [-]Embryonic cardio-respiratory impairments in rainbow trout (Oncorhynchus mykiss) following exposure to hydraulic fracturing flowback and produced water
2022
Folkerts, Erik J. | Snihur, Katherine N. | Zhang, Yifeng | Martin, Jonathan W. | Alessi, Daniel S. | Goss, Greg G.
During hydraulic fracturing, wastewaters - termed flowback and produced water (FPW) - are created as a by-product during hydrocarbon extraction. Given the large volumes of FPW that a single well can produce, and the history of FPW release to surface water bodies, it is imperative to understand the hazards that hydraulic fracturing and FPW pose to aquatic biota. Using rainbow trout embryos as model organisms, we investigated impacts to cardio-respiratory system development and function following acute (48 h) and sub-chronic (28-day) FPW exposure by examining occurrences of developmental deformities, rates of embryonic respiration (MO₂), and changes in expression of critical cardiac-specific genes. FPW-exposed embryos had significantly increased rates of pericardial edema, yolk-sac edema, and tail/trunk curvatures at hatch. Furthermore, when exposed at three days post-fertilization (dpf), acute 5% FPW exposures significantly increased embryonic MO₂ through development until 15 dpf, where a switch to significantly reduced MO₂ rates was subsequently recorded. A similar trend was observed during sub-chronic 1% FPW exposures. Interestingly, at certain specific developmental timepoints, previous salinity exposure seemed to affect embryonic MO₂; a result not previously observed. Following acute FPW exposures, embryonic genes for cardiac development and function were significantly altered, although at termination of sub-chronic exposures, significant changes to these same genes were not found. Together, our evidence of induced developmental deformities, modified embryonic MO₂, and altered cardiac transcript expression suggest that cardio-respiratory tissues are toxicologically targeted following FPW exposure in developing rainbow trout. These results may be helpful to regulatory bodies when developing hazard identification and risk management protocols concerning hydraulic fracturing activities.
اظهر المزيد [+] اقل [-]Acute and developmental toxic effects of mono-halogenated and halomethyl naphthalenes on zebrafish (Danio rerio) embryos: Cardiac malformation after 2-bromomethyl naphthalene exposure
2022
Park, Jungeun | Kim, Yurim | Jeon, Hwang-Ju | Kim, Kyeongnam | Kim, Chaeeun | Lee, Seungki | Son, Jino | Lee, Sung-Eun
Polyhalogenated polycyclic aromatic hydrocarbons (HPAHs) represent a major environmental concern due to their persistency and toxicity. Among them, mono-halogenated (HNs) and halomethyl naphthalenes (HMNs) are not well-studied, and the toxicity of many HNs to fishes has not been reported. In this study, we exposed zebrafish (Danio rerio) embryos to naphthalene and five HNs at concentrations ranging from 0.25 to 2.0 mg L⁻¹ to assess acute toxicities and developmental effects. Among them, 2-bromomethyl naphthalene (2-BMN) produced moderate lethal effects (96-h LC₅₀ = 1.4 mg L⁻¹) and significantly reduced hatchability. Abnormal phenotypes, including pericardial edema, spine curvature, and shortened body length, were also induced by 2-BMN (96-h EC₅₀ = 0.45 mg L⁻¹). Treatments of 0.5–2.0 mg L⁻¹ 2-BMN evoked cardiac malformations via significant down-regulation of the cacna1c gene, which codes the voltage-dependent calcium channel, at 72 hpf and up-regulation of the nppa gene, responsible for the expression of natriuretic peptides, at 96 hpf in zebrafish. One presumable toxic photo-dissociated metabolite of 2-BMN, the 2-naphthylmethyl radical, may be responsible for the toxic effect on zebrafish embryos. HPAHs must be monitored and managed due to their adverse effects on living organisms at low concentrations.
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