scholarly journals Zebrafish Embryos and Larvae as Alternative Animal Models for Toxicity Testing

2021 ◽  
Vol 22 (24) ◽  
pp. 13417
Author(s):  
Benedikt Bauer ◽  
Angela Mally ◽  
Daniel Liedtke
Keyword(s):  
Toxicity Testing ◽  
Biological Properties ◽  
Alternative Methods ◽  
Zebrafish Embryos ◽  
Laboratory Methods ◽  
Potential Harm ◽  
Toxicological Studies ◽  
Laboratory Investigations ◽  
Genetic Techniques ◽  
Free Feeding

Prerequisite to any biological laboratory assay employing living animals is consideration about its necessity, feasibility, ethics and the potential harm caused during an experiment. The imperative of these thoughts has led to the formulation of the 3R-principle, which today is a pivotal scientific standard of animal experimentation worldwide. The rising amount of laboratory investigations utilizing living animals throughout the last decades, either for regulatory concerns or for basic science, demands the development of alternative methods in accordance with 3R to help reduce experiments in mammals. This demand has resulted in investigation of additional vertebrate species displaying favourable biological properties. One prominent species among these is the zebrafish (Danio rerio), as these small laboratory ray-finned fish are well established in science today and feature outstanding biological characteristics. In this review, we highlight the advantages and general prerequisites of zebrafish embryos and larvae before free-feeding stages for toxicological testing, with a particular focus on cardio-, neuro, hepato- and nephrotoxicity. Furthermore, we discuss toxicokinetics, current advances in utilizing zebrafish for organ toxicity testing and highlight how advanced laboratory methods (such as automation, advanced imaging and genetic techniques) can refine future toxicological studies in this species.

scholarly journals To the problems of toxicity testing of nanorized objects (Literature review)

2021 ◽  
Vol 90 (1) ◽  
pp. 75-80
Author(s):  
OB Leonenko
Keyword(s):  
Biological Effects ◽  
Chorioallantoic Membrane ◽  
Toxicity Testing ◽  
Aquatic Organisms ◽  
Alternative Methods ◽  
Laboratory Animals ◽  
Scientific Publications ◽  
Toxicological Studies ◽  
Analytical Review

Aim of the Research. To present and summarize data on the problems of assessing the toxicity and hazards of nanosized particles due to the peculiarities of their activity and variability, which prove the need to develop a vector of research in vitro. Materials and Methods. Targeted testing can provide broad coverage of nanoproducts, reduce the cost and time of research, as well as the number of animals used in experiments. Various model test systems are proposed for use, the use of which is possible to detect harmful effects of man-made nanomaterials, and also for other chemicals: cellular and subcellular elements (mitochondria, microsomes, DNA, chorioallantoic membrane vessels), organs of laboratory animals, the simplest (unicellular) organisms, microorganisms, various aquatic organisms, plants, insects, sperm of cattle. Biotesting is one of the methods of research in the field of toxicology, used to determine the degree of toxic effects of chemical, physical and biologically unfavorable factors that are potentially dangerous to humans and components of ecosystems. An analytical review of scientific publications was carried out using the abstract databases of scientific libraries Pub Med, Medline and text databases of scientific publishing houses Elsevier, Pub Med, Central, BMJ group as well as other VIP databases. Results and Conclusions. Recently, publications emphasize that the manifestations of biological effects depend on changes in the characteristics and properties of nanomaterials. These facts cannot be taken into account in standard toxicological studies. One of the ways to intensify tests and reduce their cost may be the use of accelerated toxicological studies on simple biological systems (models). In this regard, the development and implementation of alternative methods in vitro has become one of the leading areas of toxicological research of nanomaterials. Key Words: nanoparticles, toxicity, testing.

Analogy Models for Prediction of Human Toxicity

1990 ◽  
Vol 18 (1_part_1) ◽  
pp. 103-116
Author(s):  
Sven Hellberg ◽  
Lennart Eriksson ◽  
Jörgen Jonsson ◽  
Fredrik Lindgren ◽  
Michael Sjöström ◽  
...  
Keyword(s):  
Human Subjects ◽  
Toxicity Testing ◽  
In Vitro Cytotoxicity ◽  
Alternative Methods ◽  
Laboratory Animals ◽  
In Vitro Tests ◽  
Human Toxicity ◽  
Efficient Data ◽  
Basal Cytotoxicity

Estimating the toxicity to humans of chemicals by testing on human subjects is not considered to be ethically acceptable, and toxicity testing on laboratory animals is also questionable. Therefore, there is a need for alternative methods that will give estimates of various aspects of human toxicity. Batteries of in vitro tests, together with physicochemical and toxicokinetic data, analysed by efficient data analytical methods, may enable analogy models to be constructed that can predict human toxicity. It may be possible to model non-specific toxicity relating to lipophilicity, or basal cytotoxicity, for a series of diverse compounds with large variation in chemical structure and physicochemical properties. However, local models for a series of similar compounds are generally expected to be more accurate, as well as being capable of modelling more-specific interactions. Analogy models for the prediction of human toxicity are discussed and exemplified with physicochemical and cytotoxicity data from the first ten chemicals in the multicenter evaluation of in vitro cytotoxicity (MEIC) project.

scholarly journals Cytochrome P450-dependent biotransformation capacities in embryonic, juvenile and adult stages of zebrafish (Danio rerio)—a state-of-the-art review

2021 ◽  
Author(s):  
Ann-Kathrin Loerracher ◽  
Thomas Braunbeck
Keyword(s):  
Cytochrome P450 ◽  
Phase I ◽  
Mrna Expression ◽  
Danio Rerio ◽  
Developmental Stages ◽  
State Of The Art ◽  
Adverse Outcome Pathway ◽  
Zebrafish Embryos ◽  
Toxicological Studies ◽  
Cyp Isoforms

AbstractGiven the strong trend to implement zebrafish (Danio rerio) embryos as translational model not only in ecotoxicological, but also toxicological testing strategies, there is an increasing need for a better understanding of their capacity for xenobiotic biotransformation. With respect to the extrapolation of toxicological data from zebrafish embryos to other life stages or even other organisms, qualitative and quantitative differences in biotransformation pathways, above all in cytochrome P450-dependent (CYP) phase I biotransformation, may lead to over- or underestimation of the hazard and risk certain xenobiotic compounds may pose to later developmental stages or other species. This review provides a comprehensive state-of-the-art overview of the scientific knowledge on the development of the CYP1-4 families and corresponding phase I biotransformation and bioactivation capacities in zebrafish. A total of 68 publications dealing with spatiotemporal CYP mRNA expression patterns, activities towards mammalian CYP-probe substrates, bioactivation and detoxification activities, as well as metabolite profiling were analyzed and included in this review. The main results allow for the following conclusions: (1) Extensive work has been done to document mRNA expression of CYP isoforms from earliest embryonic stages of zebrafish, but juvenile and adult zebrafish have been largely neglected so far. (2) There is insufficient understanding of how sex- and developmental stage-related differences in expression levels of certain CYP isoforms may impact biotransformation and bioactivation capacities in the respective sexes and in different developmental stages of zebrafish. (3) Albeit qualitatively often identical, many studies revealed quantitative differences in metabolic activities of zebrafish embryos and later developmental stages. However, the actual relevance of age-related differences on the outcome of toxicological studies still needs to be clarified. (4) With respect to current remaining gaps, there is still an urgent need for further studies systematically assessing metabolic profiles and capacities of CYP isoforms in zebrafish. Given the increasing importance of Adverse Outcome Pathway (AOP) concepts, an improved understanding of CYP capacities appears essential for the interpretation and outcome of (eco)toxicological studies.

scholarly journals Evaluation of Alternative Methods to Assess the Biological Properties of Propolis on Metabolic Activity and Biofilm Formation in Streptococcus mutans

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Jorge Jesús Veloz ◽  
Marysol Alvear ◽  
Luis A. Salazar
Keyword(s):  
Flow Cytometry ◽  
Confocal Microscopy ◽  
Streptococcus Mutans ◽  
Metabolic Activity ◽  
Crystal Violet ◽  
Biofilm Formation ◽  
Biological Activities ◽  
Biological Properties ◽  
Alternative Methods ◽  
Flow Cytometry Analysis

Several biological activities have been reported for the Chilean propolis, among their antimicrobial and antibiofilm properties, due to its high polyphenol content. In this study, we evaluate alternative methods to assess the effect of Chilean propolis on biofilm formation and metabolic activity of Streptococcus mutans (S. mutans), a major cariogenic agent in oral cavity. Biofilm formation was studied by using crystal violet and by confocal microscopy. The metabolic activity of biofilm was evaluated by MTT and by flow cytometry analysis. The results show that propolis reduces biofilm formation and biofilm metabolic activity in S. mutans. When the variability of the methods to measure biofilm formation was compared, the coefficient of variation (CV) fluctuated between 12.8 and 23.1% when using crystal violet methodology. On the other hand, the CV ranged between 2.2 and 3.3% with confocal microscopy analysis. The CV for biofilm’s metabolic activity measured by MTT methodology ranged between 5.0 and 11.6%, in comparison with 1.9 to 3.2% when flow cytometry analysis was used. Besides, it is possible to conclude that the methods based on colored compounds presented lower precision to study the effect of propolis on biofilm properties. Therefore, we recommend the use of flow cytometry and confocal microscopy in S. mutans biofilm analysis.

Integrated Decision-tree Testing Strategies for Environmental Toxicity with Respect to the Requirements of the EU REACH Legislation

2008 ◽  
Vol 36 (1_suppl) ◽  
pp. 29-42 ◽  
Author(s):  
Christina Grindon ◽  
Robert Combes ◽  
Mark T.D. Cronin ◽  
David W. Roberts ◽  
John F. Garrod
Keyword(s):  
Risk Assessment ◽  
Decision Tree ◽  
Aquatic Toxicity ◽  
Toxicity Testing ◽  
Threshold Concentration ◽  
Alternative Methods ◽  
The European Union ◽  
Animal Testing ◽  
Testing Strategies

Liverpool John Moores University and FRAME recently conducted a research project sponsored by Defra on the status of alternatives to animal testing with regard to the European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for safety testing and risk assessment of chemicals. The project covered all the main toxicity endpoints associated with the REACH system. This paper focuses on the prospects for using alternative methods (both in vitro and in silico) for environmental (aquatic) toxicity testing. The manuscript reviews tests based on fish cells and cell lines, fish embryos, lower organisms, and the many expert systems and QSARs for aquatic toxicity testing. Ways in which reduction and refinement measures can be used are also discussed, including the Upper Threshold Concentration — Step Down (UTC) approach, which has recently been retrospectively validated by ECVAM and subsequently endorsed by the ECVAM Scientific Advisory Committee (ESAC). It is hoped that the application of this approach could reduce the number of fish used in acute toxicity studies by around 65–70%. Decision-tree style integrated testing strategies are also proposed for acute aquatic toxicity and chronic toxicity (including bioaccumulation), followed by a number of recommendations for the future facilitation of aquatic toxicity testing with respect to environmental risk assessment.

scholarly journals DISRUPTION OF PROTEIN COMPLEXES

2013 ◽  
Vol 11 (03) ◽  
pp. 1341008 ◽  
Author(s):  
GOLNAZ TAHERI ◽  
MAHNAZ HABIBI ◽  
LIMSOON WONG ◽  
CHANGIZ ESLAHCHI
Keyword(s):  
Protein Complexes ◽  
Biological Properties ◽  
Alternative Methods ◽  
Biological Processes ◽  
Biological Functions ◽  
Yeast Protein ◽  
Minimal Set ◽  
Connection Degree ◽  
Minimum Number ◽  
Molecular Machinery

Protein complexes are a cornerstone of many biological processes and, together, they form various types of molecular machinery that perform a vast array of biological functions. Different complexes perform different functions and, the same complex can perform very different functions that depend on a variety of factors. Thus disruption of protein complexes can be lethal to an organism. It is interesting to identify a minimal set of proteins whose removal would lead to a massive disruption of protein complexes and, to understand the biological properties of these proteins. A method is presented for identifying a minimum number of proteins from a given set of complexes so that a maximum number of these complexes are disrupted when these proteins are removed. The method is based on spectral bipartitioning. This method is applied to yeast protein complexes. The identified proteins participate in a large number of biological processes and functional modules. A large proportion of them are essential proteins. Moreover, removing these identified proteins causes a large number of the yeast protein complexes to break into two fragments of nearly equal size, which minimizes the chance of either fragment being functional. The method is also superior in these aspects to alternative methods based on proteins with high connection degree, proteins whose neighbors have high average degree, and proteins that connect to lots of proteins of high connection degree. Our spectral bipartitioning method is able to efficiently identify a biologically meaningful minimal set of proteins whose removal causes a massive disruption of protein complexes in an organism.

Periprocedural Bleeding Risk Assessment in Chronic Liver Disease

2017 ◽  
Vol 01 (04) ◽  
pp. 306-312
Author(s):  
Brett Fortune ◽  
David Madoff ◽  
Benjamin May
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Blood Product ◽  
Bleeding Risk ◽  
International Normalized Ratio ◽  
Chronic Liver ◽  
Alternative Methods ◽  
Advanced Liver Disease ◽  
Potential Harm ◽  
Clotting Disorder

AbstractInvasive procedures are common in the management of cirrhosis-related chronic liver disease (CLD). Assessing bleeding risk prior to these procedures is challenging because of commonly seen laboratory abnormalities among traditional testing used to evaluate bleeding risk in patients with advanced liver disease. However, this ‘coagulopathy’ seen in advanced liver disease is not a true bleeding or clotting disorder. The prothrombin time/international normalized ratio (PT/INR) test is frequently elevated in CLD patients, but has been shown to poorly correlate with bleeding risk in this population. A traditional interpretation of this laboratory test can lead to unnecessary transfusion of blood product, procedure delay, or even potential harm to the patient. An understanding of the ‘coagulopathy’ of advanced liver disease and alternative methods, to more accurately assess bleeding risk, allows clinicians to treat safely CLD patients.

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