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Size-dependent impact of polystyrene microplastics on the toxicity of cadmium through altering neutrophil expression and metabolic regulation in zebrafish larvae
2021
Qin, Li | Duan, Zhenghua | Cheng, Haodong | Wang, Yudi | Zhang, Haihong | Zhu, Zhe | Wang, Lei
Insufficient evidence exists regarding the visible physiological toxic endpoints of MPs exposures on zebrafish larvae due to their small sizes. Herein, the impacts of micro-polystyrene particles (μ-PS) and 100 nm polystyrene particles (n-PS) on the toxicity of cadmium (Cd) through altering neutrophil expressions were identified and quantified in the transgenic zebrafish (Danio rerio) larvae Tg(lyz:DsRed2), and the effects were size-dependent. When exposed together with μ-PS, the amount of neutrophils in Cd treated zebrafish larvae decreased by 25.56% through reducing Cd content in the larvae. By contrast, although n-PS exposure caused lower Cd content in the larvae, the expression of neutrophils under their combined exposure remained high. The mechanism of immune toxicity was analyzed based on the results of metabonomics. n-PS induced high oxidative stress in the larvae, which promoted taurine metabolism and unsaturated fatty biosynthesis in n-PS + Cd treatment. This observation was accordance with the significant inhibition of the activities of superoxide dismutase and catalase enzymes detected in their combined treatment. Moreover, n-PS promoted the metabolic pathways of catabolic processes, amino acid metabolism, purine metabolism, and steroid hormone biosynthesis in Cd treated zebrafish larvae. Nanoplasctis widely coexist with other pollutants in the environment at relatively low concentrations. We conclude that more bio-markers of immune impact should be explored to identify their toxicological mechanisms and mitigate the effects on the environment.
Mostrar más [+] Menos [-]Differential mitochondrial dysregulation by exposure to individual organochlorine pesticides (OCPs) and their mixture in zebrafish embryos
2021
Lee, Hyojin | Ko, Eun | Shin, Sooim | Choi, Moonsung | Kim, Ki-Tae
Organochlorine pesticides (OCPs) have been reported to cause mitochondrial dysfunction. However, most studies reported its mitochondrial toxicity with respect to a single form, which is far from the environmentally relevant conditions. In this study, we exposed zebrafish embryos to five OCPs: chlordane, heptachlor, p,p’-dichlorodiphenyltrichloroethane (p,p’-DDT), β-hexachlorocyclohexane (β-HCH), and hexachlorobenzene (HCB), as well as an equal ratio mixture of these OCPs. We evaluated mitochondrial function, including oxygen consumption, the activity of mitochondrial complexes, antioxidant reactions, and expression of genes involved in mitochondrial metabolism. Oxygen consumption rate was reduced by exposure to chlordane, and β-HCH, linking to the increased activity of specific mitochondrial complex I and III, and decreased GSH level. We found that these mitochondrial dysfunctions were more significant in the exposure to the OCP mixture than the individual OCPs. On the mRNA transcription level, the individual OCPs mainly dysregulated the metabolic cycle (i.e., cs and acadm), whereas the OCP mixture disrupted the genes related to mitochondrial oxidative phosphorylation (i.e., sdha). Consequently, we demonstrate that the OCP mixture disrupts mitochondrial metabolism by a different molecular mechanism than the individual OCPs, which warrants further study to evaluate mitochondrial dysregulation by chronic exposure to the OCP mixture.
Mostrar más [+] Menos [-]Developmental exposures to perfluorooctanesulfonic acid (PFOS) impact embryonic nutrition, pancreatic morphology, and adiposity in the zebrafish, Danio rerio
2021
Sant, Karilyn E. | Annunziato, Kate | Conlin, Sarah | Teicher, Gregory | Chen, Phoebe | Venezia, Olivia | Downes, Gerald B. | Park, Yeonhwa | Timme-Laragy, Alicia R.
Perfluorooctanesulfonic acid (PFOS) is a persistent environmental contaminant previously found in consumer surfactants and industrial fire-fighting foams. PFOS has been widely implicated in metabolic dysfunction across the lifespan, including diabetes and obesity. However, the contributions of the embryonic environment to metabolic disease remain uncharacterized. This study seeks to identify perturbations in embryonic metabolism, pancreas development, and adiposity due to developmental and subchronic PFOS exposures and their persistence into later larval and juvenile periods. Zebrafish embryos were exposed to 16 or 32 μM PFOS developmentally (1–5 days post fertilization; dpf) or subchronically (1–15 dpf). Embryonic fatty acid and macronutrient concentrations and expression of peroxisome proliferator-activated receptor (PPAR) isoforms were quantified in embryos. Pancreatic islet morphometry was assessed at 15 and 30 dpf, and adiposity and fish behavior were assessed at 15 dpf. Concentrations of lauric (C12:0) and myristic (C14:0) saturated fatty acids were increased by PFOS at 4 dpf, and PPAR gene expression was reduced. Incidence of aberrant islet morphologies, principal islet areas, and adiposity were increased in 15 dpf larvae and 30 dpf juvenile fish. Together, these data suggest that the embryonic period is a susceptible window of metabolic programming in response to PFOS exposures, and that these early exposures alone can have persisting effects later in the lifecourse.
Mostrar más [+] Menos [-]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.
Mostrar más [+] Menos [-]Toxicity and fate of chiral insecticide pyriproxyfen and its metabolites in zebrafish (Danio rerio)
2021
Wei, Yimu | Cui, Jingna | Zhai, Wangjing | Liu, Xueke | Zhou, Zhiqiang | Wang, Peng | Liu, Donghui
Pyriproxyfen is a juvenile hormone analogue insecticide used worldwide. At present, the potential threat of pyriproxyfen to aquatic organism has not been well explored. In this work, the bioaccumulation, metabolic profile and toxicity of pyriproxyfen and its metabolites to zebrafish were studied, and the enantioselectivity of pyriproxyfen and the major chiral metabolites were also determined. Sixteen metabolites of pyriproxyfen in zebrafish were identified. Hydroxylation, ether linkage cleavage and oxidation in phase I metabolism, followed by sulfate and glucuronic acid conjugation. The bioconcentration factors ranged from 1175 to 1246. Hydroxylation metabolites of pyriproxyfen showed enantioselective behavior in zebrafish with enantiomer fractions (EFs) of 4′–OH– pyriproxyfen and 5″–OH– pyriproxyfen ranged from 0.50 to 0.71. Toxicological indexes including acute toxicity, joint toxicity and oxidative stress were tested. Among all the metabolites, 4′–OH– pyriproxyfen was found 2 folds more toxic to zebrafish than pyriproxyfen. (−)-Pyriproxyfen was found 2 folds more toxic than rac- and (+)-pyriproxyfen. Antagonistic effects were found in binary joint toxicity of pyriproxyfen and its hydroxylated metabolites. Pyriproxyfen and its metabolites also showed oxidative stress damage by inhibiting the activity of CAT and SOD and increasing MDA. This work provided deep insight into the metabolism and the potential risks of pyriproxyfen to aquatic organisms.
Mostrar más [+] Menos [-]Bioconcentration and developmental neurotoxicity of novel brominated flame retardants, hexabromobenzene and pentabromobenzene in zebrafish
2021
Chen, Xiangping | Guo, Wei | Lei, Lei | Guo, Yongyong | Yang, Lihua | Han, Jian | Zhou, Bingsheng
The flame retardants hexabromobenzene (HBB) and pentabromobenzene (PBB) have been extensively used and become ubiquitous pollutants in the aquatic environment and biota, but their potential toxic effects on wildlife remained unknown. In this study, by using zebrafish (Danio rerio) as a model, the bioconcentration and developmental neurotoxicity were investigated. Zebrafish embryos were exposed to HBB and PBB (0, 30, 100 and 300 μg/L) from 2 until 144 h post-fertilization (hpf). Chemical analysis showed bioconcentrations of both chemicals, while HBB is readily metabolized to PBB in zebrafish larvae. Embryonic exposure to both chemicals did not cause developmental toxicity, but induced locomotor behavioral anomalies in larvae. Molecular docking results indicated that both chemicals could bind to zebrafish acetylcholinesterase (AChE). Furthermore, HBB and PBB significantly inhibited AChE activities, accompanied by increased contents of acetylcholine and decreased choline in larvae. Downregulation of the genes associated with central nervous system (CNS) development (e.g., mbp, α1-tubulin, gfap, shha) as well as the corresponding proteins (e.g., Mbp, α1-Tubulin) was observed, but gap-43 was upregulated at both gene and protein levels. Together, our results indicate that both HBB and PBB exhibit developmental neurotoxicity by affecting various parameters related to CNS development and indications for future toxicological research and risk assessment of the novel brominated flame retardants.
Mostrar más [+] Menos [-]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.
Mostrar más [+] Menos [-]Screening of potential oestrogen receptor α agonists in pesticides via in silico, in vitro and in vivo methods
2021
Shen, Chao | Zhu, Kongyang | Ruan, Jinpeng | Li, Jialing | Wang, Yi | Zhao, Meirong | He, Chengyong | Zuo, Zhenghong
In modern agricultural management, the use of pesticides is indispensable. Due to their massive use worldwide, pesticides represent a latent risk to both humans and the environment. In the present study, 1056 frequently used pesticides were screened for oestrogen receptor (ER) agonistic activity by using in silico methods. We found that 72 and 47 pesticides potentially have ER agonistic activity by the machine learning methods random forest (RF) and deep neural network (DNN), respectively. Among endocrine-disrupting chemicals (EDCs), 14 have been reported as EDCs or ER agonists by previous studies. We selected 3 reported and 7 previously unreported pesticides from 76 potential ER agonists to further assess ERα agonistic activity. All 10 selected pesticides exhibited ERα agonistic activity in human cells or zebrafish. In the dual-luciferase reporter gene assays, six pesticides exhibited ERα agonistic activity. Additionally, nine pesticides could induce mRNA expression of the pS2 and NRF1 genes in MCF-7 cells, and seven pesticides could induce mRNA expression of the vtg1 and vtg2 genes in zebrafish. Importantly, the remaining 48 out of 76 potential ER agonists, none of which have previously been reported to have endocrine-disrupting effects or oestrogenic activity, should be of great concern. Our screening results can inform environmental protection goals and play an important role in environmental protection and early warnings to human health.
Mostrar más [+] Menos [-]Probiotics inhibit the stunted growth defect of perfluorobutanesulfonate via stress and thyroid axes in zebrafish larvae
2021
Perfluorobutanesulfonate (PFBS) is an emerging pollutant in aquatic environments and potently disrupts the early developmental trajectory of teleosts. Considering the persistent and toxic nature of PFBS, it is necessary to develop in situ protective measures to ameliorate the toxic damage of PFBS. Probiotic supplements are able to mitigate the growth retardation defects of PFBS. However, the interactive mechanisms remain elusive. To this end, this study acutely exposed zebrafish larvae to a concentration gradient of PFBS (0, 1, 3.3 and 10 mg/L) for 4 days, during which probiotic bacteria Lactobacillus rhamnosus were added in the rearing water. After exposure, alterations in gene transcriptions and key hormones along the hypothalamus–pituitary–interrenal (HPI), growth hormone/insulin–like growth factor (GH/IGF) and hypothalamus–pituitary–thyroid (HPT) axes were examined. The results showed that PFBS single exposure significantly increased the cortisol concentrations, suggesting the induction of stress response, while probiotic supplementation effectively decreased the cortisol levels in coexposed larvae in an attempt to relieve the stress of PFBS toxicant. It was unexpected that probiotic additive significantly decreased the larval GH concentrations independent of PFBS, thereby eliminating the contribution of GH/IGF axis to the growth improvement of probiotics. In contrast, probiotic bacteria remarkably increased the concentration of thyroid hormones, particularly the thyroxine (T4), in zebrafish larvae. The pronounced down-regulation of uridinediphosphate glucoronosyltransferases (UDPGT) gene pointed to the blocked elimination process of T4 by probiotics. Furthermore, proteomic fingerprinting found that probiotics were potent to shape the protein expression pattern in PFBS-exposed zebrafish larvae and modulated multiple biological processes that are essential for the growth. In summary, the present findings suggest that HPI and HPT axes may cooperate to enhance the growth of fish larvae under PFBS and probiotic coexposures.
Mostrar más [+] Menos [-]6-benzylaminopurine exposure induced development toxicity and behaviour alteration in zebrafish (Danio rerio)
2021
Yang, Mengying | Qiu, Jinyu | Zhao, Xin | Feng, XiZeng
6-benzylaminopurine (6-BA) is one of the first synthetic hormones and has been widely used in fruit cultivation, gardening and agriculture. However, excessive use of 6-BA will cause potential harm to the environment and humans. Therefore, our research focused on assessing the impact of 6-BA on the development and neurobehavior of zebrafish. The results showed that 6-BA had little effect on the embryos from 2 hpf to 10 hpf. However, delayed development, decreased survival and hatchability were observed under 30 and 40 mg/L 6-BA from 24 hpf. 6-BA also reduced surface tension of embryonic chorions at 24 hpf. In addition, 6-BA caused abnormal morphology and promoted the accumulation of oxidative stress. Transcription of genes in connection with development and oxidative stress was also strikingly altered. Results of movement assay showed that zebrafish were less active and their behavior was significantly inhibited under the 20 and 30 mg/L 6-BA treatments. Locomotion-related genes th and mao were down-regulated by gradient, while the transcription of dbh was upregulated at a low concentration (2 mg/L) but decreased as the concentration increased. Moreover, 6-BA exposure caused increased arousal and decreased sleep. Sleep/wake related genes hcrt and hcrtr2 were upregulated, but decreased at 30 mg/L, while the mRNA level of aanat2 was reduced in a concentration-dependent manner. To sum up, our results showed that 6-BA induced developmental toxicity, promoted the accumulation of oxidative stress, and damaged locomotion and sleep/wake behavior.
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