Evaluation and comparison of the mitochondrial and developmental toxicity of three strobilurins in zebrafish embryo/larvae

Yang, Lihua; Huang, Tao; Li, Ruiwen; Souders, Christopher L.; Rheingold, Spencer; Tischuk, Claire; Li, Na; Zhou, Bingsheng; Martyniuk, Christopher J.

doi:10.1016/j.envpol.2020.116277

Cited by 24 publications

(10 citation statements)

References 43 publications

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“…The mitochondrial stress test has been used successfully to assess mitochondrial dysfunction due to chemical exposure in zebrafish embryos/larvae. , In current study, embryonic exposure to 400 μg/L DBDPE could significantly inhibit OCRs in zebrafish larvae (Figure A). The nonmitochondrial respiratory test showed no obvious changes in all DBDPE-treated groups.…”

Section: Results and Discussionmentioning

confidence: 73%

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Mitochondrial Dysfunction Was Involved in Decabromodiphenyl Ethane-Induced Glucolipid Metabolism Disorders and Neurotoxicity in Zebrafish Larvae

Yang,

Zhu,

Zhou

et al. 2023

Environ. Sci. Technol.

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Decabromodiphenyl ethane (DBDPE), a novel brominated flame retardant, is becoming increasingly prevalent in environmental and biota samples. While DBDPE has been shown to cause various biological adverse effects, the molecular mechanism behind these effects is still unclear. In this research, zebrafish embryos were exposed to DBDPE (50–400 μg/L) until 120 h post fertilization (hpf). The results confirmed the neurotoxicity by increased average swimming speed, interfered neurotransmitter contents, and transcription of neurodevelopment-related genes in zebrafish larvae. Metabolomics analysis revealed changes of metabolites primarily involved in glycolipid metabolism, oxidative phosphorylation, and oxidative stress, which were validated through the alterations of multiple biomarkers at various levels. We further evaluated the mitochondrial performance upon DBDPE exposure and found inhibited mitochondrial oxidative respiration accompanied by decreased mitochondrial respiratory chain complex activities, mitochondrial membrane potential, and ATP contents. However, addition of nicotinamide riboside could effectively restore DBDPE-induced mitochondrial impairments and resultant neurotoxicity, oxidative stress as well as glycolipid metabolism in zebrafish larvae. Taken together, our data suggest that mitochondrial dysfunction was involved in DBDPE-induced toxicity, providing novel insight into the toxic mechanisms of DBDPE as well as other emerging pollutants.

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Section: Results and Discussionmentioning

confidence: 73%

“…Each well contained one larva and 500 μL of bath water. Then, the oxygen consumption rates (OCRs) were assessed using a Seahorse XF24 extracellular flux analyzer (Agilent Technologies Inc., CA, USA) according to previously reported methods. , Please refer to the Supporting Information (Text S5) for more specific details.…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial Dysfunction Was Involved in Decabromodiphenyl Ethane-Induced Glucolipid Metabolism Disorders and Neurotoxicity in Zebrafish Larvae

Yang,

Zhu,

Zhou

et al. 2023

Environ. Sci. Technol.

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“…The pMoA of an increased cost for maintenance is in line with the MoA of the TFS fungicide compound, which targets the mitochondrial respiratory pathways. This MoA has been observed also on nontarget organisms, such as zebrafish embryos (Yang et al, 2021). Therefore, we consider the combination of increased cost for maintenance and no feedback to be most plausible.…”

Section: Model Calibrationmentioning

confidence: 76%

Environmental Risk Assessment with Energy Budget Models: A Comparison Between Two Models of Different Complexity

Romoli,

Jager,

Trijau

et al. 2023

Environmental Toxicology and Chemistry

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The extrapolation of effects from controlled standard laboratory tests to real environmental conditions is a major challenge facing Ecological Risk Assessment (ERA) of chemicals. Toxicokinetic‐Toxicodynamic (TKTD) models, such as those based on Dynamic Energy Budget (DEB) theory, can play an important role in filling this gap. Through the years, different practical TKTD models have been derived from DEB theory, ranging from the full ‘standard’ DEB animal model to simplified ‘DEBtox’ models. It is currently unclear what impact a different level of model complexity can have on the regulatory risk assessment. In this study, we compare the performance of two DEB‐TKTD models with different level of complexity, focussing on model calibration on standard test data and on forward‐predictions for untested time‐variable exposure profiles. The first model is based on the standard DEB model with primary parameters (stdDEB‐TKTD) whereas the second is a reduced version with compound parameters, based on DEBkiss (DEBtox2019). After harmonisation of the modelling choices, we demonstrate that these two models can achieve very similar performances both in the calibration and in the forward prediction step. With the data presented in this study, selection of the most‐suitable TKTD model for ERA therefore cannot be based alone on goodness‐of‐fit nor on the precision of model predictions (within current ERA procedures for pesticides), but would likely be based on the trade‐off between ease of use and model flexibility. We also stress the importance of modelling choices, such as how to fill gaps in the information content of experimental toxicity data, and how to accommodate differences in growth and reproduction between different data sets for the same chemical‐species combination.

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“…Research on β-methoxyacrylate pesticides is limited to toxicity, resistance, and other undesirable side effects. − To overcome these limitations, a few suggestions and possible research directions for future work are provided as follows: (1) structural modifications of the side chain can be always efficient means for the development of novel β-methoxyacrylate pesticides to avoid resistance; (2) synthesis of hybrids by combining the β-methoxyacrylate pharmacophores and other active substructures might lead to novel β-methoxyacrylate pesticides; (3) combination β-methoxyacrylate fungicides with other fungicides such as SDHIs and DMIs can be another effective strategy to prevent resistance; (4) computational approaches such as fragment-based drug discovery (FBDD) and pharmacophore-linked fragment virtual screening (PFVS) should be utilized in order to discover novel β-methoxyacrylate pesticides with diverse structures.…”

Section: Summary and Future Prospectsmentioning

confidence: 99%

Comprehensive Overview of β-Methoxyacrylate Derivatives as Cytochrome bc₁ Inhibitors for Novel Pesticide Discovery

Luo

Ning

Rao

2022

J. Agric. Food Chem.

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β-Methoxyacrylate derivatives represent a new class of pesticides, which have attracted increasing attention owing to their unique structure, broad biological activity, and unique mechanisms of action. They inhibit mitochondrial respiration via preventing electron transfer at the Qo site of the cytochrome bc 1 complex and thus are identified as cyt bc 1 inhibitors. A variety of βmethoxyacrylate derivatives have been reported by many research groups for discovery of novel pesticides with improved expected activities. This review focuses on development of β-methoxyacrylate derivatives with great significance as pesticides such as fungicides, acaricides, insecticides, herbicides, and antiviral agents. In addition, the structure−activity relationships (SARs) of βmethoxyacrylate derivatives are summarized. Moreover, the cause of resistance to β-methoxyacrylate fungicides and some solutions are also introduced. Finally, the development trend of β-methoxyacrylate derivatives as pesticides is explored. We hope the review will give a guide to develop novel β-methoxyacrylate pesticides in the future.

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Evaluation and comparison of the mitochondrial and developmental toxicity of three strobilurins in zebrafish embryo/larvae

Cited by 24 publications

References 43 publications

Mitochondrial Dysfunction Was Involved in Decabromodiphenyl Ethane-Induced Glucolipid Metabolism Disorders and Neurotoxicity in Zebrafish Larvae

Mitochondrial Dysfunction Was Involved in Decabromodiphenyl Ethane-Induced Glucolipid Metabolism Disorders and Neurotoxicity in Zebrafish Larvae

Environmental Risk Assessment with Energy Budget Models: A Comparison Between Two Models of Different Complexity

Comprehensive Overview of β-Methoxyacrylate Derivatives as Cytochrome bc₁ Inhibitors for Novel Pesticide Discovery

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Evaluation and comparison of the mitochondrial and developmental toxicity of three strobilurins in zebrafish embryo/larvae

Cited by 24 publications

References 43 publications

Mitochondrial Dysfunction Was Involved in Decabromodiphenyl Ethane-Induced Glucolipid Metabolism Disorders and Neurotoxicity in Zebrafish Larvae

Mitochondrial Dysfunction Was Involved in Decabromodiphenyl Ethane-Induced Glucolipid Metabolism Disorders and Neurotoxicity in Zebrafish Larvae

Environmental Risk Assessment with Energy Budget Models: A Comparison Between Two Models of Different Complexity

Comprehensive Overview of β-Methoxyacrylate Derivatives as Cytochrome bc1 Inhibitors for Novel Pesticide Discovery

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Product

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Comprehensive Overview of β-Methoxyacrylate Derivatives as Cytochrome bc₁ Inhibitors for Novel Pesticide Discovery