The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Kechun Liu - One of the best experts on this subject based on the ideXlab platform.

  • Psoralen Induces Developmental Toxicity in Zebrafish Embryos/Larvae Through Oxidative Stress, Apoptosis, and Energy Metabolism Disorder
    Frontiers Media S.A., 2018
    Co-Authors: Qing Xia, Yun Zhang, Liwen Han, Lingying Wei, Haotian Kong, Yongping Shi, Xue Wang, Xiqiang Chen, Kechun Liu
    Abstract:

    Psoralen Toxicity is an issue of wide concern. However, an assay for psoralen-induced Developmental Toxicity has not been reported to date. Moreover, the underlying mechanism of psoralen-induced Developmental Toxicity is unclear. Therefore, this study attempted to develop a psoralen-induced Developmental Toxicity assay in zebrafish embryos/larvae. Psoralen treatment caused a decrease in the hatching rate and body length and a significant increase in the malformation rate of zebrafish. Yolk retention, pericardial edema, swim-bladder deficiency, and curved body shape were also observed after psoralen treatment. Yolk retention might have been caused by an abnormality in lipid metabolism. Further experiments indicated that psoralen exerted toxic effects on the developing heart, liver, phagocytes, and nervous system. Increased generation of reactive oxygen species, inhibition of total superoxide dismutase activity, and increased malondialdehyde concentrations indicated inhibition of antioxidant capacity and the presence of oxidative stress. A greater number of apoptotic cells were observed after psoralen exposure, relative to the control. Furthermore, the results of gene-expression analysis showed that psoralen induced Developmental Toxicity by means of oxidative stress, apoptosis, and energy metabolism abnormalities. These findings will be helpful in understanding psoralen-induced Toxicity

  • Developmental Toxicity and cardiac effects of butyl benzyl phthalate in zebrafish embryos
    Aquatic Toxicology, 2017
    Co-Authors: Guijin Sun, Kechun Liu
    Abstract:

    Phthalic acid esters (PAEs), commonly called phthalates, have become ubiquitous environment pollutants. Studies have focused on reproductive Toxicity, neuroToxicity, teratogenicity, tumourigenesis, and mutagenesis of phthalates. However, relatively little is known about the phthalates effects on the heart. Butyl benzyl phthalate (BBP), a member of PAEs, is classified by the US Environmental Protection Agency as a priority environmental pollutant. We studied the Developmental Toxicity of BBP, especially its effects on the heart development, in zebrafish (Danio rerio) embryos. Embryos at 4hr post-fertilization (hpf) were exposed to 0, 0.1, 0.6 and 1.2mg/L BBP until 72hpf. BBP caused abnormalities in embryo morphology, including yolk-sac edema, spinal curvature, tail deformity, uninflated swim bladder and cardiac defects. Exposure to 0.6mg/L BBP significantly increased the malformation rate, caused growth inhibition, increased the cardiac malformation rate as well as the distance between the sinus venosus (SV) and bulbus arteriosus (BA), and reduced the heart rate of embryos. Exposure to 1.2mg/L BBP significantly affected all endpoints, except survival rate at 24hpf. To preliminarily elucidate the potential mechanism of heart Developmental Toxicity caused by BBP, we examined the expression of two genes related to heart development, Nkx2.5 and T-box transcription factor 5, by real-time quantitative PCR. The expression of the two genes was dose-dependently downregulated with BBP. BBP could induce Developmental Toxicity, with adverse effects on the heart development in zebrafish embryos, and alter the expression of genes related to heart development.

  • oxidative stress mediated Developmental Toxicity induced by isoniazide in zebrafish embryos and larvae
    Journal of Applied Toxicology, 2017
    Co-Authors: Yu Zou, Yun Zhang, Liwen Han, Hairong Hou, Jian Han, Ximin Wang, Juan Cen, Kechun Liu
    Abstract:

    Isoniazide (INH) is an important first-line drug that is used to treat tuberculosis. However, the effect of INH on fetal growth has not yet been elucidated, and the mechanism of INH-induced Developmental Toxicity is still unknown. In the present study, we employed zebrafish embryos and larvae to investigate the Developmental Toxicity of INH. The survival rates of the embryos and larvae as well as the hatching rates of embryos were significantly reduced. Morphological abnormalities, including spinal curvature, yolk retention, swimming bladder absence, tail bending and shorter body lengths were induced by INH. Histopathological analysis showed loose cell-to-cell contacts and large vacuoles in the larval hepatocytes. Thin intestinal walls, frayed gut villi and widespread cell lysis were observed in the intestines of the larvae in the higher concentration (8, 16 mm) exposure groups. In addition, exposure to high doses (≥ 6 mm) of INH significantly reduced the locomotor capacity of the zebrafish larvae. INH significantly increased the levels of reactive oxygen species and malondialdehyde and decreased the superoxide dismutase activity in zebrafish larvae, which suggested that oxidative stress was induced and that the antioxidant capacity was inhibited. Superoxide dismutase 1 and liver fatty acid-binding protein mRNA levels were significantly downregulated, while the GSTP2 and cytochrome P450 3A mRNA levels were significantly upregulated in the INH-exposed zebrafish larvae. The overall results indicated that INH caused a dose- and time-dependent increase in Developmental Toxicity and that oxidative stress played an important role in the Developmental Toxicity induced by INH in zebrafish larvae. Copyright © 2017 John Wiley & Sons, Ltd.

B Zhou - One of the best experts on this subject based on the ideXlab platform.

  • evaluation and comparison of the mitochondrial and Developmental Toxicity of three strobilurins in zebrafish embryo larvae
    Environmental Pollution, 2021
    Co-Authors: B Zhou, Lihua Yang, Tao Huang, Christopher L Souders, Spencer Rheingold, Claire Tischuk, Christopher J Martyniuk
    Abstract:

    Abstract Strobilurin fungicides have been frequently detected in aquatic environments and can induce mitochondrial Toxicity to non-target aquatic organisms. However, the derived Toxicity and subsequent mechanisms related to their adverse effects are not fully elucidated. In the present study, we compared the mitochondrial and Developmental Toxicity of azoxystrobin, pyraclostrobin, and trifloxystrobin using zebrafish embryo/larvae. The results showed that all three strobilurins inhibited mitochondrial and non-mitochondrial respiration (the potency is pyraclostrobin ≈ trifloxystrobin > azoxystrobin). Behavioral changes indicated that sublethal doses of pyraclostrobin and azoxystrobin caused hyperactivity of zebrafish larvae in dark cycles, whereas trifloxystrobin resulted in hypoactivity of zebrafish larvae. In addition, pyraclostrobin exposure impaired the inflation of swim bladder, and caused down-regulation of annexin A5 (anxa5) mRNA levels, and up-regulated transcript levels of pre-B-cell leukemia homeobox 1a (pbx1a); conversely, azoxystrobin and trifloxystrobin did not cause detectable effects with swim bladder inflation. Molecular docking results indicated that azoxystrobin had higher interacting potency with iodotyrosine deiodinase (IYD), prolactin receptor (PRLR), antagonistic conformation of thyroid hormone receptor β (TRβ) and glucocorticoid receptor (GR) compared to pyraclostrobin and trifloxystrobin; pyraclostrobin and azoxystrobin were more likely to interact with the antagonistic conformation of TRβ and GR, respectively. These results may partially explain the different effects observed in behavior and swim bladder inflation, and also point to potential endocrine disruption induced by these strobilurins. Taken together, our study revealed that all three strobilurins alter mitochondrial bioenergetics and cause Developmental Toxicity. However, the toxic phenotypes and underlying mechanisms of each chemical may differ, and this requires further investigation. Pyraclostrobin showed higher mitochondrial Toxicity at lethal doses and higher Developmental Toxicity at sublethal doses compared to the two other strobilurins tested. These results provide novel information for toxicological study as well as risk assessment of strobilurin fungicides.

  • hexabromocyclododecane induced Developmental Toxicity and apoptosis in zebrafish embryos
    Aquatic Toxicology, 2009
    Co-Authors: Jun Deng, Paul K S Lam, Chunsheng Liu, Xiongjie Shi, Leo W Y Yeung, B Zhou
    Abstract:

    Hexabromocyclododecane (HBCD) is widely used as a brominated flame retardant, and has been detected in the aquatic environment, wild animals, and humans. However, details of the environmental health risk of HBCD are not well known. In this study, zebrafish embryos were used to assess the Developmental Toxicity of the chemical. Four-hour post-fertilization (hpf) zebrafish embryos were exposed to various concentrations of HBCD (0, 0.05, 0.1, 0.5, and 1.0 mg L-1) until 96 h. Exposure to 0.1, 0.5, and 1.0 mg L-1 HBCD significantly increased the malformation rate and reduced survival in the 0.5 and 1.0 mg L-1 HBCD exposure groups. Acridine orange (AO) staining showed that HBCD exposure resulted in cell apoptosis. Reactive oxygen species (ROS) was significantly induced at exposures of 0.1, 0.5, and 1.0 mg L-1 HBCD. To test the apoptotic pathway, several genes related to cell apoptosis, such as p53, Puma, Apaf-1, caspase-9, and caspase-3, were examined using real-time PCR. The expression patterns of these genes were up-regulated to some extent. Two anti-apoptotic genes, Mdm2 (antagonist of p53) and Bcl-2 (inhibitor of Bax), were down-regulated, and the activity of capspase-9 and caspase-3 was significantly increased. The overall results demonstrate that waterborne HBCD is able to produce oxidative stress and induce apoptosis through the involvement of caspases in zebrafish embryos. The results also indicate that zebrafish embryos can serve as a reliable model for the Developmental Toxicity of HBCD. (C) 2009 Elsevier B.V. All rights reserved.

  • Developmental Toxicity and alteration of gene expression in zebrafish embryos exposed to pfos
    Toxicology and Applied Pharmacology, 2008
    Co-Authors: Xiongjie Shi, Paul K S Lam, B Zhou
    Abstract:

    Perfluorooctanesulfonate (PFOS) is a persistent organic pollutant, the potential Toxicity of which is causing great concern. In the present study, we employed zebrafish embryos to investigate the Developmental Toxicity of this compound. Four-hour post-fertilization (hpf) zebrafish embryos were exposed to 0.1, 0.5, 1, 3 and 5 mg/L PFOS. Hatching was delayed and hatching rates as well as larval survivorship were significantly reduced after the embryos were exposed to 1, 3 and 5 mg/L PFOS until 132 hpf. The fry displayed gross Developmental malformations, including epiboly deformities, hypopigmentation, yolk sac edema, tail and heart malformations and spinal curvature upon exposure to PFOS concentrations of 1 mg/L or greater. Growth (body length) was significantly reduced in the 3 and 5 mg/L PFOS-treated groups. To test whether Developmental malformation was mediated via apoptosis, flow cytometry analysis of DNA content, acridine orange staining and TUNEL assay was used. These techniques indicated that more apoptotic cells were present in the PFOS-treated embryos than in the control embryos. Certain genes related to cell apoptosis, p53 and Bax, were both significantly up-regulated upon exposure to all the concentrations tested. In addition, we investigated the effects of PFOS on marker genes related to early thyroid development (hhex and pax8) and genes regulating the balance of androgens and estrogens (cyp19a and cyp19b). For thyroid development, the expression of hhex was significantly up-regulated at all concentrations tested, whereas pax8 expression was significantly up-regulated only upon exposure to lower concentrations of PFOS (0.1, 0.5, 1 mg/L). The expression of cyp19a and of cyp19b was significantly down-regulated at all exposure concentrations. The overall results indicated that zebrafish embryos constitute a reliable model for testing the Developmental Toxicity of PFOS, and the gene expression patterns in the embryos were able to reveal some potential mechanisms of Developmental Toxicity.

Richard E Peterson - One of the best experts on this subject based on the ideXlab platform.

  • reproductive and Developmental Toxicity of dioxin in fish
    Molecular and Cellular Endocrinology, 2012
    Co-Authors: Tisha C Kingheiden, Warren Heideman, Vatsal Mehta, Kong M Xiong, Kevin A Lanham, Dagmara S Antkiewicz, Alissa M Ganser, Richard E Peterson
    Abstract:

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin) is a global environmental contaminant and the prototypical ligand for investigating aryl hydrocarbon receptor (AHR)-mediated Toxicity. Environmental exposure to TCDD results in Developmental and reproductive Toxicity in fish, birds and mammals. To resolve the ecotoxicological relevance and human health risks posed by exposure to dioxin-like AHR agonists, a vertebrate model is needed that allows for Toxicity studies at various levels of biological organization, assesses adverse reproductive and Developmental effects and establishes appropriate integrative correlations between different levels of effects. Here we describe the reproductive and Developmental Toxicity of TCDD in feral fish species and summarize how using the zebrafish model to investigate TCDD Toxicity has enabled us to characterize the AHR signaling in fish and to better understand how dioxin-like chemicals induce Toxicity. We propose that such studies can be used to predict the risks that AHR ligands pose to feral fish populations and provide a platform for integrating risk assessments for both ecologically relevant organisms and humans.

  • Developmental Toxicity of low generation pamam dendrimers in zebrafish
    Toxicology and Applied Pharmacology, 2007
    Co-Authors: Tisha King C Heiden, Warren Heideman, Emelyne Dengler, Weiyuan John Kao, Richard E Peterson
    Abstract:

    Biological molecules and intracellular structures operate at the nanoscale; therefore, development of nanomedicines shows great promise for the treatment of disease by using targeted drug delivery and gene therapies. PAMAM dendrimers, which are highly branched polymers with low polydispersity and high functionality, provide an ideal architecture for construction of effective drug carriers, gene transfer devices and imaging of biological systems. For example, dendrimers bioconjugated with selective ligands such as Arg-Gly-Asp (RGD) would theoretically target cells that contain integrin receptors and show potential for use as drug delivery devices. While RGD-conjugated dendrimers are generally considered not to be cytotoxic, there currently exists little information on the risks that such materials pose to human health. In an effort to compliment and extend the knowledge gleaned from cell culture assays, we have used the zebrafish embryo as a rapid, medium throughput, cost-effective whole-animal model to provide a more comprehensive and predictive Developmental Toxicity screen for nanomaterials such as PAMAM dendrimers. Using the zebrafish embryo, we have assessed the Developmental Toxicity of low generation (G3.5 and G4) PAMAM dendrimers, as well as RGD-conjugated forms for comparison. Our results demonstrate that G4 dendrimers, which have amino functional groups, are toxic and attenuate growth and development of zebrafish embryos at sublethal concentrations; however, G3.5 dendrimers, with carboxylic acid terminal functional groups, are not toxic to zebrafish embryos. Furthermore, RGD-conjugated G4 dendrimers are less potent in causing embryo Toxicity than G4 dendrimers. RGD-conjugated G3.5 dendrimers do not elicit Toxicity at the highest concentrations tested and warrant further study for use as a drug delivery device.

  • understanding dioxin Developmental Toxicity using the zebrafish model
    Birth Defects Research Part A-clinical and Molecular Teratology, 2006
    Co-Authors: Sara A Carney, Amy L Prasch, Warren Heideman, Richard E Peterson
    Abstract:

    Zebrafish (Danio rerio) have advantages over mammals as an animal model for investigating Developmental Toxicity. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (dioxin, TCDD), a persistent global contaminant, is the most comprehensively studied Developmental toxicant in zebrafish. The hallmark responses of TCDD Developmental Toxicity manifested in zebrafish larvae include edema, anemia, hemorrhage, and ischemia associated with arrested growth and development. Heart and vasculature development and function are severely impaired, and jaw malformations occur secondary to inhibited chondrogenesis. The swim bladder fails to inflate, and the switch from embryonic to adult erythropoiesis is blocked. This profile of Developmental Toxicity responses, commonly referred to as "blue sac syndrome" because the edematous yolk sac appears blue, is observed in the larval form of all freshwater fish species exposed to TCDD at the embryonic stage of development. Components of the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator (AHR/ARNT) signaling pathway in zebrafish have been identified and functionally characterized. Their role in mediating TCDD Toxicity has been determined using morpholinos to specifically knockdown the translation of zfAHR1, zfAHR2, zfARNT1, and zfARNT2 mRNAs, respectively, and a line of zfARNT2 null mutant zebrafish has provided further insight. These studies have shown that zfAHR2 and zfARNT1 mediate TCDD Developmental Toxicity. In addition, the growing use of molecular and genomic tools for research on zebrafish have led to advances in our understanding of the mechanism of TCDD Developmental Toxicity at the molecular level, including the recent finding that Toxicity is not mediated by increased cytochrome P4501A (zfCYP1A) expression.

  • aryl hydrocarbon receptor 2 mediates 2 3 7 8 tetrachlorodibenzo p dioxin Developmental Toxicity in zebrafish
    Toxicological Sciences, 2003
    Co-Authors: Amy L Prasch, Sara A Carney, Warren Heideman, Wu Dong, Hiroki Teraoka, Takeo Hiraga, John J Stegeman, Richard E Peterson
    Abstract:

    In order to use the zebrafish as a model vertebrate to investigate the Developmental Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), it is essential to know whether one or both forms of the zebrafish aryl hydrocarbon receptor (AHR), zfAHR1 or zfAHR2, mediate Toxicity. To determine the role of zfAHR2, an antisense morpholino approach was used to knock down translation of the protein. No effect of the zfahr2 morpholino (zfahr2-MO) was seen on normal development in embryos not treated with TCDD. Injection of embryos at the 1-2 cell stage with zfahr2-MO decreased TCDD-induced transcription of zfCYP1A mRNA until 96 h post fertilization (hpf), and immuno-histochemical detection of zfCYP1A protein in embryos at 72 hpf revealed a dramatic decrease in expression. The zfahr2-MO completely protected embryos from TCDD-induced edema and anemia and provided protection against TCDD-induced reductions in peripheral blood flow initially; however, a slight reduction in blood flow was observed at later times when the morpholino was no longer effective. Due to persistence of TCDD and decreasing effectiveness of the zfahr2-MO over time, the morpholino provided only transient protection against TCDD-induced inhibition of chondrogenesis of the lower jaw, and no protection against an effect of TCDD that was initiated late in development, blockade of swimbladder inflation. The zfahr2-MO did not protect embryos from TCDD-induced mortality but did produce a 48 h delay in its onset. Endpoints of TCDD Developmental Toxicity manifested in zfahr2 morphants at late stages of development, beyond 144 hpf, were clearly different from TCDD-exposed embryos injected with a control morpholino. Most strikingly, zfahr2 morphants exposed to TCDD never developed edema. Taken together, these results demonstrate that zfAHR2 mediates several endpoints of TCDD Developmental Toxicity in zebrafish.

Yu Zou - One of the best experts on this subject based on the ideXlab platform.

  • oxidative stress mediated Developmental Toxicity induced by isoniazide in zebrafish embryos and larvae
    Journal of Applied Toxicology, 2017
    Co-Authors: Yu Zou, Yun Zhang, Liwen Han, Hairong Hou, Jian Han, Ximin Wang, Juan Cen, Kechun Liu
    Abstract:

    Isoniazide (INH) is an important first-line drug that is used to treat tuberculosis. However, the effect of INH on fetal growth has not yet been elucidated, and the mechanism of INH-induced Developmental Toxicity is still unknown. In the present study, we employed zebrafish embryos and larvae to investigate the Developmental Toxicity of INH. The survival rates of the embryos and larvae as well as the hatching rates of embryos were significantly reduced. Morphological abnormalities, including spinal curvature, yolk retention, swimming bladder absence, tail bending and shorter body lengths were induced by INH. Histopathological analysis showed loose cell-to-cell contacts and large vacuoles in the larval hepatocytes. Thin intestinal walls, frayed gut villi and widespread cell lysis were observed in the intestines of the larvae in the higher concentration (8, 16 mm) exposure groups. In addition, exposure to high doses (≥ 6 mm) of INH significantly reduced the locomotor capacity of the zebrafish larvae. INH significantly increased the levels of reactive oxygen species and malondialdehyde and decreased the superoxide dismutase activity in zebrafish larvae, which suggested that oxidative stress was induced and that the antioxidant capacity was inhibited. Superoxide dismutase 1 and liver fatty acid-binding protein mRNA levels were significantly downregulated, while the GSTP2 and cytochrome P450 3A mRNA levels were significantly upregulated in the INH-exposed zebrafish larvae. The overall results indicated that INH caused a dose- and time-dependent increase in Developmental Toxicity and that oxidative stress played an important role in the Developmental Toxicity induced by INH in zebrafish larvae. Copyright © 2017 John Wiley & Sons, Ltd.

Nicole C Deziel - One of the best experts on this subject based on the ideXlab platform.

  • A systematic evaluation of chemicals in hydraulic-fracturing fluids and wastewater for reproductive and Developmental Toxicity
    Journal of Exposure Science & Environmental Epidemiology, 2017
    Co-Authors: Elise G Elliott, Adrienne S Ettinger, Brian P Leaderer, Michael B Bracken, Nicole C Deziel
    Abstract:

    Hydraulic-fracturing fluids and wastewater from unconventional oil and natural gas development contain hundreds of substances with the potential to contaminate drinking water. Challenges to conducting well-designed human exposure and health studies include limited information about likely etiologic agents. We systematically evaluated 1021 chemicals identified in hydraulic-fracturing fluids ( n =925), wastewater ( n =132), or both ( n =36) for potential reproductive and Developmental Toxicity to triage those with potential for human health impact. We searched the REPROTOX database using Chemical Abstract Service registry numbers for chemicals with available data and evaluated the evidence for adverse reproductive and Developmental effects. Next, we determined which chemicals linked to reproductive or Developmental Toxicity had water quality standards or guidelines. Toxicity information was lacking for 781 (76%) chemicals. Of the remaining 240 substances, evidence suggested reproductive Toxicity for 103 (43%), Developmental Toxicity for 95 (40%), and both for 41 (17%). Of these 157 chemicals, 67 had or were proposed for a federal water quality standard or guideline. Our systematic screening approach identified a list of 67 hydraulic fracturing-related candidate analytes based on known or suspected Toxicity. Incorporation of data on potency, physicochemical properties, and environmental concentrations could further prioritize these substances for future drinking water exposure assessments or reproductive and Developmental health studies.

  • a systematic evaluation of chemicals in hydraulic fracturing fluids and wastewater for reproductive and Developmental Toxicity
    Journal of Exposure Science and Environmental Epidemiology, 2017
    Co-Authors: Elise G Elliott, Adrienne S Ettinger, Brian P Leaderer, Michael B Bracken, Nicole C Deziel
    Abstract:

    A systematic evaluation of chemicals in hydraulic-fracturing fluids and wastewater for reproductive and Developmental Toxicity