The food preservative ethoxyquin impairs zebrafish development, behavior and alters gene expression profile (original) (raw)
Related papers
Teratological Effects of a Panel of Sixty Water-Soluble Toxicants on Zebrafish Development
Zebrafish, 2014
The zebrafish larva is a promising whole-animal model for safety pharmacology, environmental risk assessment, and developmental toxicity. This model has been used for the high-throughput toxicity screening of various compounds. Our aim here is to identify possible phenotypic markers of teratogenicity in zebrafish embryos that could be used for the assaying compounds for reproductive toxicity. We have screened a panel of 60 water-soluble toxicants to examine their effects on zebrafish development. A total of 22,080 wild-type zebrafish larvae were raised in 250 lL defined buffer in 96-well plates at a plating density of one embryo per well. They were exposed for a 96-h period starting at 24 h post-fertilization. A logarithmic concentration series was used for range-finding, followed by a narrower geometric series for developmental toxicity assessment. A total of 9017 survivors were analyzed at 5 days post-fertilization for nine phenotypes, namely, (1) normal, (2) pericardial oedema, (3) yolk sac oedema, (4) melanophores dispersed, (5) bent tail tip, (6) bent body axis, (7) abnormal Meckel's cartilage, (8) abnormal branchial arches, and (9) uninflated swim bladder. For each toxicant, the EC 50 (concentration required to produce one or more of these abnormalities in 50% of embryos) was also calculated. For the majority of toxicants (55/60) there was, at the population level, a statistically significant, concentration-dependent increase in the incidence of abnormal phenotypes among survivors. The commonest abnormalities were pericardial oedema, yolk sac oedema, dispersed melanophores, and uninflated swim bladder. It is possible therefore that these could prove to be general indicators of reproductive toxicity in the zebrafish embryo assay.
Reproductive toxicology (Elmsford, N.Y.), 2013
Zebrafish developmental toxicity testing is an emerging field, which faces considerable challenges regarding data meta-analysis and the establishment of standardized test protocols. Here, we present an initial correlation study on toxicity of 133 chemicals based on data in the literature to ascertain predictive developmental toxicity endpoints. We found that the physical properties of chemicals (BCF or log P) did not fully predict lethality or developmental outcomes. Instead, individual outcomes such as pericardial edema and yolk sac edema were more reliable indicators of developmental toxicity. In addition, we ranked the chemicals based on toxicity with the Toxicological Priority Index (ToxPi) program and via a teratogenic ratio, and found that perfluorooctane sulfonate (PFOS) had the highest ToxPi score, triphenyltin acetate had the highest average ToxPi score (corrected for missing data and having more than 4 outcomes), and N-methyl-dithiocarbamate had the highest teratogenic ratio.
Neurotoxicology and Teratology, 2014
Androgens, which act through the androgen receptor (AR), regulate 77 male sexual development; however little information is available on 78 its role during embryonic development (Gorelick et al., 2008). In 79 zebrafish, only one AR (gene ar) has been identified (Hossain et al., 80 2008; Jorgensen et al., 2007). Previous studies have indicated that 81 both estrogens and androgens could act as apoptotic signaling mod-82 ulators (Acconcia et al., 2005; Simões et al., 2013; Song and Santen, 83 2003). Apoptosis is a physiological mechanism of cell death that plays 84 an essential role in the maintenance of tissue homeostasis and in the 85 embryonic development . Considering this,
Reproductive toxicology (Elmsford, N.Y.), 2014
With the high cost and slow pace of toxicity testing in mammals, the vertebrate zebrafish has become a tractable model organism for high throughput toxicity testing. We present here a meta-analysis of 600 chemicals tested for toxicity in zebrafish embryos and larvae. Nineteen aggregated and 57 individual toxicity endpoints were recorded from published studies yielding 2695 unique data points. These data points were compared to lethality and reproductive toxicology endpoints analyzed in rodents and rabbits and to exposure values for humans. We show that although many zebrafish endpoints did not correlate to rodent or rabbit acute toxicity data, zebrafish could be used to accurately predict relative acute toxicity through the rat inhalation, rabbit dermal, and rat oral exposure routes. Ranking of the chemicals based on toxicity and teratogenicity in zebrafish, as well as human exposure levels, revealed that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), benzo(a)pyrene, and chlorpyrifos r...
Toxicity effects of profenofos on embryonic and larval development of Zebrafish (Danio rerio)
Environmental Toxicology and Pharmacology, 2015
The aim of the present study was to evaluate the developmental toxicity of profenofos to early developing Zebrafish (Danio rerio) embryos (4 h post fertilization) in a static system at 1.0 to 2.25 mg/L. Median lethal concentrations (LC 50) of profenofos at 24-h, 48-h, 72-h and 96-h were determined as 2.04, 1.58, 1.57 and 1.56 mg/L, respectively. The hatching of embryos were recorded at every 12 h interval and the median hatching time (HT 50) was also calculated for each concentration. In a separate set of experiments, 96-h LC 10 (0.74 mg/L) and LC 50 (1.56 mg/L) concentrations were used to assess the developmental toxicity in relation to behavior, morphology, and interactions with the targeted enzyme acetylcholinesterase. Live videomicroscopy revealed that the profenofos exposed embryos exhibited an abnormal development, skeletal defects and altered heart morphology in a concentration-dependent manner, which leads to alterations in the swimming behavior of hatchlings at 144-h,which indicate that developing zebrafish are sensitive to profenofos.
Aquatic Toxicology, 2008
The main effluent from oil and gas production is produced water (PW), a waste that contains low to moderate concentrations of oil-derived substances such as polycyclic aromatic hydrocarbons (PAHs) and alkylphenols (APs). PW components may be present in seawater at low concentrations over large areas in the vicinity of oil and gas production facilities. In this study, zebrafish (Danio rerio) were exposed to control and three treatments (high-, pulsed-, low-dose) of a synthetic PW mixture for 1, 7 and 13 weeks. The aim was to investigate the development of transcriptome and biomarker responses as well as relationships between early responses and population-relevant effects. The synthetic PW contained a mixture of low-molecular-weight PAHs (<5 ring) and short-chain APs (C1-C4). The water-borne exposure levels (sum PAH) ranged from 0.54 ppb (low dose) to 5.4 ppb (high dose). Bile pyrene metabolites ranged from 17-133 ng g −1 bile in the control group to 23-1081 ng g −1 bile in the high exposure group. Similar levels have been observed in wild fish, confirming an environmentally relevant exposure. The expression of mRNAs of hepatic genes was investigated in the high exposure group using the Zebrafish OligoLibrary TM from Compugen. Functional clustering analysis revealed effects in the reproductive system, the nervous system, the respiratory system, the immune system, lipid metabolism, connective tissue and in a range of functional categories related to cell cycle and cancer. The majority of differentially expressed mRNAs of genes were down-regulated, suggesting reduction in gene transcription to be as relevant as up-regulation or induction when assessing biological responses to PW exposure. Biomarkers for effects of PAHs (cytochrome P450 1A) and environmental estrogens (vitellogenin) did not appear to be affected by the chronic exposure to low concentration of PW components. Effects at the population level included a reduction in condition factor in male fish from all exposed groups and spinal column deformations in the F1 generation of exposed groups. The different exposure regimes did not produce any significant differences in reproduction or recruitment. The results from this study demonstrate that environmentally relevant concentrations of PW affect gene expression and population-relevant endpoints in zebrafish, although links between the two were not obvious.
Journal of Student Research
Pharmaceutical chemicals are being produced, consumed, and excreted in human civilization at an increasing rate. These chemicals have the capacity to accumulate, especially in environments such as freshwater systems, but there have not been any major responses to this threat yet as the present concentrations of the chemicals is not viewed as dangerous. Previous research has shown that the developing concentrations of chemicals is an issue, supporting that these chemicals, though not present in large doses, have impacts on exposed organisms. However, prior research has not been conducted to examine the specific effects of chemicals at hormetic concentrations on freshwater organisms. “Hormetic concentration” defines the concentrations of chemicals at specific levels where the response to a low dose of chemical differs from the response to the high dose, and these were the ranges of concentration that were tested in this experiment. Zebrafish were acquired at zero days post fertilizat...
Differential gene expression as a toxicant-sensitive endpoint in zebrafish embryos and larvae
Aquatic Toxicology, 2007
The zebrafish (Danio rerio) embryo toxicity test (DarT) is under consideration as an alternative to the acute fish toxicity test. Microscopically visible developmental disorders or death are the endpoints used to report on toxicity in DarT. These endpoints are easily observed. They, however, rarely reveal mechanisms leading to a toxic effect and are relatively insensitive compared to chronic toxic effects. We hypothesized that, by using gene expression profiles as an additional endpoint, it may be possible to increase the sensitivity and predictive value of DarT. Therefore, as a proof of principle, we exposed zebrafish embryos to the reference compound 3,4-dichloroaniline (3,4-DCA) and analyzed gene expression patterns with a 14k oligonucleotide array. Important stress response genes not included in the microarray were additionally quantified by reverse transcriptase polymerase chain reaction. Six genes involved in biotransformation (cyp1a, ahr2), stress response (nfe212, maft, hmox1) and cell cycle control (fzr1) were significantly regulated. With the exception of fzr1, these genes proved to be differentially expressed in post hatch life stages as well. The identified genes point toward an aryl hydrocarbon receptor-mediated response. Differential gene expression in embryos exposed for 48 h was observed at 3,4-DCA concentrations as low as 0.78 M, which is more than 10-fold below the concentrations that elicited visible toxic effects. Upon exposure for 5 days, differential expression was detected at concentrations as low as 0.22 M of 3,4-DCA, which was close to the lowest observed effect concentration (0.11 M) in the 30-day early life stage test. This study therefore indicates that gene expression analysis in DarT is able to reveal mechanistic information and may also be exploited for the development of replacement methods for chronic fish tests.
Chemosphere, 2018
The mode of action (MOA) plays a key role in the risk assessment of pollutants in water. Although fish is a key model organism used in the risk assessment of pollutants in water, the MOAs have not been compared between fish and embryo toxicity for classified compounds. In this paper, regression analysis was carried out for fish and embryo toxicities against the calculated molecular descriptors and MOAs were evaluated from toxicity ratio. The toxicity significantly related with the chemical hydrophobicity for baseline and less inert compounds, respectively, indicates that these two classes of compounds share the same MOAs between fish and embryos. Comparison of the toxicity ratios shows that reactive compounds exhibit excess toxicity to both fish and embryos. These compounds can react covalently with biologically target molecules through nucleophilic addition reactions, Michael addition oxidation, or amination. Comparing with baseline, less inert and reactive compounds, many specific...