MS-222 induces biochemical and transcriptional changes related to oxidative stress, cell proliferation and apoptosis in zebrafish embryos

Félix, Luís; Luzio, Ana; Santos, Ana Caroline dos; Antunes, Luís; Coimbra, Ana M.; Valentim, Ana M.

doi:10.1016/j.cbpc.2020.108834

Cited by 11 publications

(3 citation statements)

References 106 publications

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“…The rationale is justified by the fact that, in apoptotic cells, acridine orange may permeate them and bind to DNA, whereas normal cells are not permeable to it [ 93 , 94 ]. This technique has been widely used to detect apoptosis in zebrafish exposed to different types of compounds [ 49 , 95 ]. The data found by AO staining showed that the highest concentration of RF could exert pro-apoptotic activity, the same concentration group that showed high levels of ROS.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory, Oxidative Stress, and Apoptosis Effects in Zebrafish Larvae after Rapid Exposure to a Commercial Glyphosate Formulation

et al. 2021

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Glyphosate-based herbicides (GBH) are the most used herbicides in the world, carrying potentially adverse consequences to the environment and non-target species due to their massive and inadequate use. This study aimed to evaluate the effects of acute exposure to a commercial formulation of glyphosate, Roundup® Flex (RF), at environmentally relevant and higher concentrations in zebrafish larvae through the assessment of the inflammatory, oxidative stress and cell death response. Transgenic Tg(mpxGFP)i114 and wild-type (WT) zebrafish larvae (72 h post-fertilisation) were exposed to 1, 5, and 10 µg mL−1 of RF (based on the active ingredient concentration) for 4 h 30 min. A concentration of 2.5 µg mL−1 CuSO4 was used as a positive control. Copper sulphate exposure showed effectiveness in enhancing the inflammatory profile by increasing the number of neutrophils, nitric oxide (NO) levels, reactive oxygen species (ROS), and cell death. None of the RF concentrations tested showed changes in the number of neutrophils and NO. However, the concentration of 10 µg a.i. mL−1 was able to induce an increase in ROS levels and cell death. The activity of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)), the biotransformation activity, the levels of reduced (GSH) and oxidised (GSSG) glutathione, lipid peroxidation (LPO), lactate dehydrogenase (LDH), and acetylcholinesterase (AChE) were similar among groups. Overall, the evidence may suggest toxicological effects are dependent on the concentration of RF, although at concentrations that are not routinely detected in the environment. Additional studies are needed to better understand the underlying molecular mechanisms of this formulation.

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Section: Discussionmentioning

confidence: 99%

Inflammatory, Oxidative Stress, and Apoptosis Effects in Zebrafish Larvae after Rapid Exposure to a Commercial Glyphosate Formulation

et al. 2021

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“…Further, we note the low MS-222 concentration used in our studies (76 µM or 20 mg/L) (Chang et al, 2012) would suggest that impacts on development might be minimal. Nevertheless, previous studies have shown that focal exposure to varying concentrations of at earlier developmental time points (before 26 hpf) leads to cartilage malformations (Félix et al, 2018) and upregulation of genes associated with apoptosis (Félix et al, 2020). There is a considerable body of literature demonstrating the negative effects of anesthesia in the developing human brain (Andropoulos, 2018), with most studies finding associations with neuronal apoptosis specifically when using anesthetics.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Autism Zebrafish Mutant Models Using a High-Throughput Larval Phenotyping Platform

Colón-Rodríguez

Uribe-Salazar

Weyenberg

et al. 2020

Front. Cell Dev. Biol.

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In recent years, zebrafish have become commonly used as a model for studying human traits and disorders. Their small size, high fecundity, and rapid development allow for more high-throughput experiments compared to other vertebrate models. Given that zebrafish share >70% gene homologs with humans and their genomes can be readily edited using highly efficient CRISPR methods, we are now able to rapidly generate mutations impacting practically any gene of interest. Unfortunately, our ability to phenotype mutant larvae has not kept pace. To address this challenge, we have developed a protocol that obtains multiple phenotypic measurements from individual zebrafish larvae in an automated and parallel fashion, including morphological features (i.e., body length, eye area, and head size) and movement/behavior. By assaying wild-type zebrafish in a variety of conditions, we determined optimal parameters that avoid significant developmental defects or physical damage; these include morphological imaging of larvae at two time points [3 days post fertilization (dpf) and 5 dpf] coupled with motion tracking of behavior at 5 dpf. As a proof-of-principle, we tested our approach on two novel CRISPR-generated mutant zebrafish lines carrying predicted null-alleles of syngap1b and slc7a5, orthologs to two human genes implicated in autism-spectrum disorder, intellectual disability, and epilepsy. Using our optimized high-throughput phenotyping protocol, we recapitulated previously published results from mouse and zebrafish models of these candidate genes. In summary, we describe a rapid parallel pipeline to characterize morphological and behavioral features of individual larvae in a robust and consistent fashion, thereby improving our ability to better identify genes important in human traits and disorders.

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“…Previous studies have shown that focal exposure to varying concentrations of MS-222 (191-574 µM) at earlier developmental time points (before 26 hpf) leads to cartilage malformations [36] and upregulation of genes associated with apoptosis [37]. There is a considerable body of literature demonstrating the negative effects of anesthesia in the developing human brain [38], with most studies finding associations with neuronal apoptosis specifically when using anesthetics.…”

Section: Discussionmentioning

confidence: 99%

Assessment of autism zebrafish mutant models using a high-throughput larval phenotyping platform

Colón-Rodríguez

Uribe-Salazar²,

Weyenberg³

et al. 2020

Preprint

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In recent years zebrafish have become commonly used as a model for studying human traits and disorders. Their small size, high fecundity, and rapid development allow for more high-throughput experiments compared to other vertebrate models. Given that zebrafish share >70% gene homologs with humans and their genomes can be readily edited using highly efficient CRISPR methods, we are now able to rapidly generate mutations impacting practically any gene of interest. Unfortunately, our ability to phenotype mutant larvae has not kept pace. To address this challenge, we have developed a protocol that obtains multiple phenotypic measurements from individual zebrafish larvae in an automated and parallel fashion, including morphological features (i.e., body length, eye area, and head size) and movement/behavior. By assaying wild-type zebrafish in a variety of conditions, we determined optimal parameters that avoid significant developmental defects or physical damage; these include morphological imaging of larvae at two time points (3 days post fertilization (dpf) and 5 dpf) coupled with motion tracking of behavior at 5 dpf. As a proof-of-principle, we tested our approach on two novel CRISPR-generated mutant zebrafish lines carrying predicted null-alleles of syngap1b and slc7a5, orthologs to two human genes implicated in autism-spectrum disorder, intellectual disability, and epilepsy. Using our optimized high-throughput phenotyping protocol, we recapitulated previously published results from mouse and zebrafish models of these candidate genes. In summary, we describe a rapid parallel pipeline to characterize morphological and behavioral features of individual larvae in a robust and consistent fashion, thereby improving our ability to better identify genes important in human traits and disorders.AUTHOR SUMMARYZebrafish (Danio rerio) are a well-established model organism for the study of neurodevelopmental disorders. Due to their small size, fast reproduction, and genetic homology with humans, zebrafish have been widely used for characterizing and screening candidate genes for many disorders, including autism-spectrum disorder, intellectual disability, and epilepsy. Although several studies have described the use of high-throughput morphological and behavioral assays, few combine multiple assays in a single zebrafish larva. Here, we optimized a platform to characterize morphometric features at two developmental time points in addition to behavioral traits of zebrafish larvae. We then used this approach to characterize two autism candidate genes (SYNGAP1 and SLC7A5) in two CRISPR-generated zebrafish null mutant models we developed in house. These data recapitulate previously published results related to enhanced seizure activity, while identifying additional defects not previously reported. We propose that our phenotyping platform represents a feasible method for maximizing the use of single zebrafish larvae in the characterization of additional mutants relevant to neurodevelopmental disorders.

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MS-222 induces biochemical and transcriptional changes related to oxidative stress, cell proliferation and apoptosis in zebrafish embryos

Cited by 11 publications

References 106 publications

Inflammatory, Oxidative Stress, and Apoptosis Effects in Zebrafish Larvae after Rapid Exposure to a Commercial Glyphosate Formulation

Inflammatory, Oxidative Stress, and Apoptosis Effects in Zebrafish Larvae after Rapid Exposure to a Commercial Glyphosate Formulation

Assessment of Autism Zebrafish Mutant Models Using a High-Throughput Larval Phenotyping Platform

Assessment of autism zebrafish mutant models using a high-throughput larval phenotyping platform

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