scholarly journals Chronic environmentally relevant levels of Simvastatin induces non-monotonic responses in Zebrafish (Danio rerio)

2018 ◽  
Author(s):  
Susana Barros ◽  
Rosa Montes ◽  
José Benito Quintana ◽  
Rosario Rodil ◽  
Ana André ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Danio Rerio ◽  
Mevalonate Pathway ◽  
Aquatic Organisms ◽  
Molecular Data ◽  
List Type ◽  
Parental Exposure ◽  
Multi Level ◽  
Dose Responses

AbstractSimvastatin (SIM), a hypocholesterolaemic compound, is among the most prescribed pharmaceuticals for cardiovascular disease prevention worldwide. Several studies have shown that acute exposure to SIM is able to produce multiple adverse effects in aquatic organisms. However, uncertainties still remain regarding the chronic effects of SIM in aquatic ecosystems. Therefore, the present study aimed to investigate the effects of SIM in the model freshwater teleost zebrafish (Danio rerio) following a chronic exposure (90 days) to environmentally relevant concentrations ranging from 8 ng/L to 1000 ng/L. This study used a multi-parametric approach integrating distinct ecological-relevant endpoints, i.e. survival, growth, reproduction and embryonic development, with biochemical markers (cholesterol and triglycerides). Furthermore, Real Time PCR was used to analyse the transcription levels of key genes involved in the mevalonate pathway (hmgcra, cyp51, and dhcr7). Globally, SIM induced several non-monotonic dose-responses; embryonic development, biochemical and molecular markers, were significantly impacted in the low-intermediate concentrations, 40 ng/L and 200 ng/L, whereas no effects were recorded for the highest tested SIM levels (1000 ng/L). Taken together, these findings expand our understanding of statins effects in teleost’s, demonstrating significant impacts at environmentally relevant concentrations. The findings highlight the importance of addressing the effects of chemicals under chronic low-level concentrations.Graphical abstractHighlightsSeveral uncertainties exist regarding simvastatin mode of action in non-target organismsThis work integrates D. rerio multi-level responses after long-term exposure to simvastatinSimvastatin impacted cholesterol/triglycerides levels and transcript levels of genes related to mevalonate pathway.Parental exposure to simvastatin induced offspring embryonic malformations.Embryonic abnormalities, biochemical and molecular data did follow a non-monotonic curve.

scholarly journals Evaluation of the Toxicity of Bisphenol A in Reproduction and Its Effect on Fertility and Embryonic Development in the Zebrafish (Danio rerio)

2022 ◽  
Vol 19 (2) ◽  
pp. 962
Author(s):  
Lilian de Paula Gonçalves Reis ◽  
Antonio Jesús Lora-Benítez ◽  
Ana Mª Molina-López ◽  
Rafael Mora-Medina ◽  
Nahúm Ayala-Soldado ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Bisphenol A ◽  
Danio Rerio ◽  
Chemical Substance ◽  
Toxic Effects ◽  
Control Group ◽  
Histopathological Study ◽  
Parental Exposure ◽  
Electron Microscopes ◽  
Histopathological Studies

Bisphenol A (BPA) is a chemical substance commonly used in the manufacture of plastic products. Its inhalation or ingestion from particles in suspension, water, and/or polluted foods can trigger toxic effects related to endocrine disruption, resulting in hormonal, reproduction, and immunological alterations in humans and animals. The zebrafish (Danio rerio) is an ideal experimental model frequently used in toxicity studies. In order to assess the toxic effects of BPA on reproduction and embryonic development in one generation after parental exposure to it, a total of 80 zebrafish, males and females, divided into four groups in duplicate (n = 20) were exposed to BPA concentrations of 500, 50, and 5 µg L−1, along with a control group. The fish were kept in reproduction aquariums for 21 days. The embryos obtained in the crosses were incubated in a BPA-free medium and observed for signs of embryotoxicity. A histopathological study (under optical and electron microscopes) was performed of adult fish gonads. The embryos of reproducers exposed to BPA were those most frequently presenting signs of embryotoxicity, such as mortality and cardiac and musculoskeletal malformations. In the histopathological studies of adult individuals, alterations were found in ovocyte maturation and in spermatazoid formation in the groups exposed to the chemical. Those alterations were directly related to BPA action, affecting fertility in both sexes, as well as the viability of their offspring, proportionally to the BPA levels to which they were exposed, so that our results provide more information by associating toxic effects on the offspring and on the next generation.

Disruption of zebrafish (Danio rerio) embryonic development after full life-cycle parental exposure to low levels of ethinylestradiol

2009 ◽  
Vol 95 (4) ◽  
pp. 330-338 ◽  
Author(s):  
J. Soares ◽  
A.M. Coimbra ◽  
M.A. Reis-Henriques ◽  
N.M. Monteiro ◽  
M.N. Vieira ◽  
...  
Keyword(s):  
Life Cycle ◽  
Embryonic Development ◽  
Danio Rerio ◽  
Parental Exposure ◽  
Full Life Cycle ◽  
Full Life ◽  
Low Levels

scholarly journals Long-term (30 days) toxicity of NiO nanoparticles for adult zebrafish Danio rerio

2014 ◽  
Vol 7 (1) ◽  
pp. 23-26 ◽  
Author(s):  
Jevgenij A. Kovrižnych ◽  
Ružena Sotníková ◽  
Dagmar Zeljenková ◽  
Eva Rollerová ◽  
Elena Szabová
Keyword(s):  
Danio Rerio ◽  
Chronic Toxicity ◽  
Negative Impact ◽  
Aquatic Organisms ◽  
Adult Zebrafish ◽  
Nio Nanoparticles ◽  
Minimum Concentration ◽  
Static Test ◽  
Nio Nps

Abstract Nickel oxide in the form of nanoparticles (NiO NPs) is extensively used in different industrial branches. In a test on adult zebrafish, the acute toxicity of NiO NPs was shown to be low, however longlasting contact with this compound can lead to its accumulation in the tissues and to increased toxicity. In this work we determined the 30-day toxicity of NiO NPs using a static test for zebrafish Danio rerio. We found the 30-day LC50 value to be 45.0 mg/L, LC100 (minimum concentration causing 100% mortality) was 100.0 mg/L, and LC0 (maximum concentration causing no mortality) was 6.25 mg/L for adult individuals of zebrafish. Considering a broad use of Ni in the industry, NiO NPs chronic toxicity may have a negative impact on the population of aquatic organisms and on food web dynamics in aquatic systems.

scholarly journals The Zebrafish (Danio Rerio) as a Novel Model to Study Folate-mthfr Interactions During Embryonic Development and Effect(s) on Long-Term Health

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1269-1269
Author(s):  
Emanuela Pannia ◽  
Xiucheng Cui ◽  
Rebecca Simonian ◽  
Rola Hammoud ◽  
Paula Ashcraft ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Danio Rerio ◽  
Metabolic Regulation ◽  
Whole Body ◽  
High Cholesterol Diet ◽  
Global Methylation ◽  
Mthfr Genotype ◽  
Cas9 Protein

Abstract Objectives Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of the bioactive folate form, 5-methyltetrahydrofolate (5MTHF). Common polymorphisms in MTHFR limits the availability of 5MTHF and high intakes of folic acid (FA, synthetic form) may exacerbate these effects. 5MTHF is an alternative supplement to FA, but the interaction of folate form and MTHFR genotype and role in programming metabolic health has not been determined. The zebrafish (Danio rerio) is a proven model system in nutrient and drug discovery studies. The objectives of this study were to: 1) develop a mthfr zebrafish mutant model using CRISPR-Cas9 technology; and 2) identify in zebrafish the relationship between folate form (FA vs 5MTHF) and mthfr genotype on early-life development and metabolic regulation. Methods To assay the function of mthfr in vivo, we used a rapid transient knock-out approach reported to recapitulate germline zebrafish loss-of-function phenotypes. Embryos were co-injected with Cas9 protein and a set of 4 guide RNAs (4gRNA) or Cas9 protein alone (control). Zero to 5 days post-fertilization (dpf), embryos were raised in standard conditions then fed a high cholesterol diet (HCD) up to 15 dpf with a fluorescent cholesteryl BODIPY-C12. The HCD was used to induce obesity as previously reported. Global DNA methylation (5-mC%) was measured at 5 dpf and whole-body and hepatic lipid accumulation and live imaging analyses performed at 15 dpf. Results Compared to control, 4gRNA mthfr zebrafish on an HCD had enlarged liver, greater accumulation of hepatic and whole body lipids and altered lipid transport. They also had 80% lower mthfr mRNA than control zebrafish. Global methylation was ∼15% higher (P = 0.06) in 4gRNA zebrafish suggesting a compensatory dependency on an alternative methyl donor pathway during embryonic development. We are now screening germline mutant carriers and assessing folate and methylation metabolites and the interaction of folate form and genotype. Conclusions The zebrafish mthfr mutant will be a valuable model to examine the mechanisms underlining mthfr-related pathologies and provide a high-throughput in vivo system to ascertain the role of different folate forms on embryonic development and long-term health. Funding Sources CIHR-INMD; EP supported by NSERC-CGS D.

scholarly journals P044 Can an electronic prescribing system ensure clear anticoagulation discharge communication?

2019 ◽  
Vol 104 (7) ◽  
pp. e2.49-e2
Author(s):  
Susie Gage
Keyword(s):  
Patient Safety ◽  
Discharge Summary ◽  
Electronic Prescribing ◽  
List Type ◽  
Heparin Infusion ◽  
National Patient Safety Agency ◽  
High Dependency ◽  
National Patient ◽  
Discharge Summaries

AimThe National Patient Safety Agency (NPSA)1 identified heparin as a major cause of adverse events associated with adverse incidents, including some fatalities. By ensuring good communication, this should be associated with risk reduction.1 The aim of this study was to ensure there is clear anticoagulation communication on discharge, from the paediatric intensive care unit (PICU) electronic prescribing system (Philips), to the paediatric cardiac high dependency unit and paediatric cardiac ward. To investigate whether the heparin regimen complies with the hospital’s anticoagulant guidelines and if there is any deviation; that this is clearly documented. To find out if there is an indication documented for the heparin regimen chosen and if there is a clear long term plan documented for the patient, after heparin cessation.MethodsA report was generated for all patients who were prescribed a heparin infusion on PICU, between 1st January 2018 and 30th June 2018, from the Philips system. All discharge summaries from the PICU Philips system were reviewed. Only paediatric cardiac patients were included that had a heparin infusion prescribed on discharge, all other discharge summaries were excluded from the study. Each discharge summary was reviewed in the anticoagulant section; for the heparin regimen chosen, whether it complies with the hospital’s anticoagulant guidelines and if there was any deviation whether this was documented. The indication documented of which heparin regimen was chosen and whether a clear long term plan was documented after heparin cessation; for example if the patient is to be transferred onto aspirin, clopidogrel, warfarin or enoxaparin.Results82 discharge summaries were reviewed over the 6 month period between 1st January 2018 and 30th June 2018; 16 were excluded as were not paediatric cardiac, leaving 66 paediatric cardiac discharge summaries that were reviewed. 45 out of 66 (68%) complied with the hospital’s heparin anticoagulation guidelines. Of the 32% that deviated from the protocol; only 33% (7 out of 21) had a reason documented. Only 50% (33) of the summaries reviewed had an indication for anticoagulation noted on the discharge summary and 91% of discharge summaries had a long term anticoagulant plan documented.ConclusionThe electronic prescribing system can help to ensure a clear anticoagulation communication as shown by 91% of the anticoagulation long term plan being clearly documented; making it a more seamless patient transfer. On the Philips PICU electronic prescribing system there is an anticoagulant section on the discharge summary that has 3 boxes that need to be completed; heparin regimen, indication and anticoagulation long term plan. However, despite these boxes; deviations from the anticoagulant protocol were poorly documented as highlighted by only 33% having the reason highlighted in the discharge summary, only 50% of the indications were documented. Despite having prompts for this information on the discharge summary, the medical staffs needs to be aware to complete this information, in order to reduce potential medication errors and risk.ReferenceThe National Patient Safety Agency (NPSA). Actions that make anticoagulant therapy safer. NPSA; March 2007.

scholarly journals Toxic or Not Toxic, That Is the Carbon Quantum Dot’s Question: A Comprehensive Evaluation with Zebrafish Embryo, Eleutheroembryo, and Adult Models

Polymers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1598
Author(s):  
Chih-Yu Chung ◽  
Yu-Ju Chen ◽  
Chia-Hui Kang ◽  
Hung-Yun Lin ◽  
Chih-Ching Huang ◽  
...  
Keyword(s):  
Zebrafish Embryo ◽  
Comprehensive Evaluation ◽  
Aquatic Organisms ◽  
Carbon Quantum Dots ◽  
Adult Zebrafish ◽  
Fish Embryo ◽  
Wide Range ◽  
Different Types ◽  
Low Toxicity

Carbon quantum dots (CQDs) are emerging novel nanomaterials with a wide range of applications and high biocompatibility. However, there is a lack of in-depth research on whether CQDs can cause acute or long-term adverse reactions in aquatic organisms. In this study, two different types of CQDs prepared by ammonia citrate and spermidine, namely CQDAC and CQDSpd, were used to evaluate their biocompatibilities. In the fish embryo acute toxicity test (FET), the LD50 of CQDAC and CQDSpd was about 500 and 100 ppm. During the stage of eleutheroembryo, the LD50 decreased to 340 and 55 ppm, respectively. However, both CQDs were quickly eliminated from embryo and eleutheroembryo, indicating a lack of bioaccumulation. Long-term accumulation of CQDs was also performed in this study, and adult zebrafish showed no adverse effects in 12 weeks. In addition, there was no difference in the hatchability and deformity rates of offspring produced by adult zebrafish, regardless of whether they were fed CQDs or not. The results showed that both CQDAC and CQDSpd have low toxicity and bioaccumulation to zebrafish. Moreover, the toxicity assay developed in this study provides a comprehensive platform to assess the impacts of CQDs on aquatic organisms in the future.

Child Money and Food Stamps: A comparative analysis of Mongolian welfare programmes in the Ger Districts of Ulaanbaatar

2020 ◽  
Vol 66 (4) ◽  
pp. 499-524
Author(s):  
Elizabeth Fox
Keyword(s):  
Participant Observation ◽  
Food Stamps ◽  
Means Testing ◽  
Economic Cycles ◽  
Funding Sources ◽  
Urban Migrants ◽  
Multi Level ◽  
Welfare Model ◽  
Level Analysis

Abstract Until recently, the Mongolian welfare system was entirely category based. However, a new food stamps programme funded by loans from the Asian Development Bank, which targets aid according to proxy means testing, has been introduced as part of the bank’s aim to push Mongolia towards a fiscally sustainable welfare model. The food stamps programme is presented as efficient and responsible in contrast to Mongolia’s universal child money programme. Based on long-term participant observation research in the ger districts of Ulaanbaatar, areas inhabited by many rural-urban migrants living in poverty, this paper compares the two programmes, interweaving street-level accounts of the experiences of residents and bureaucrats alike with the respective histories and funding sources of the two programmes. Doing so provides a multi-level analysis of the emergent welfare state in Mongolia, unpicking the ‘system’ that ger district residents encounter, linking the relative influence of international financial institutions to democratic and economic cycles, and offering a critique of the supposed efficiency of targeted welfare programmes.

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