Exposure to pyrimethanil induces developmental toxicity and cardiotoxicity in zebrafish

Meng, Yunlong; Zhong, Keyuan; Xiao, Jianghong; Huang, Yong; Wang, You; Tang, Lin; Chen, Suping; Wu, Juan; Ma, Jinze; Cao, Zigang; Liao, Xinjun; Lu, Huiqiang

doi:10.1016/j.chemosphere.2020.126889

Cited by 64 publications

(23 citation statements)

References 63 publications

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“…36 Previous studies have shown that an abnormality of the pericardium paralyzed heart functions, resulting in arrhythmia and circulatory disorders. 37,38 Consistent with transcriptomic predictions of cardiac dysfunction, significant sublethal impacts were observed that ranged from reduced heart rate (26.9 ± 6.0% reduction at 100 μg/L) and cardiac output (85.5 ± 8.7% reduction at 100 μg/ L) to a dysregulation of cardiac development pathway genes in PFOSA exposure treatments, which was consistent with the adverse effects of PFOS on marine medaka cardiac functions. 18 PFOA exposure caused abnormal cardiac morphology and contractive rhythms attributed to cardiomyocyte injury in developing chicken hearts, 39 suggesting cardiomyocyte impairment is likely responsible for cardiac contraction disturbances, including arrhythmia, bradycardia, and heart failure following PFOSA exposure.…”

Section: Discussionsupporting

confidence: 70%

Perfluorooctane Sulfonamide (PFOSA) Induces Cardiotoxicity via Aryl Hydrocarbon Receptor Activation in Zebrafish

Chen

Zheng

Yang

et al. 2022

Environ. Sci. Technol.

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Perfluorooctane sulfonamide (PFOSA), a precursor of perfluorooctanesulfonate (PFOS), is widely used during industrial processes, though little is known about its toxicity, particularly to early life stage organisms that are generally sensitive to xenobiotic exposure. Here, following exposure to concentrations of 0.01, 0.1, 1, 10, and 100 μg/L PFOSA, transcriptional, morphological, physiological, and biochemical assays were used to evaluate the potential effects on aquatic organisms. The top Tox functions in exposed zebrafish were related to cardiac diseases predicted by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Ingenuity Pathway Analysis (IPA) analysis. Consistent with impacts predicted by transcriptional changes, abnormal cardiac morphology, disordered heartbeat signals, as well as reduced heart rate and cardiac output were observed following the exposure of 0.1, 1, 10, or 100 μg/L PFOSA. Furthermore, these PFOSA-induced cardiac effects were either prevented or alleviated by supplementation with an aryl hydrocarbon receptor (AHR) antagonist or ahr2-morpholino knock-down, uncovering a seminal role of AHR in PFOSA-induced cardiotoxicity. Our results provide the first evidence in fish that PFOSA can impair proper heart development and function and raises concern for PFOSA analogues in the natural environment.

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Section: Discussionsupporting

confidence: 70%

Perfluorooctane Sulfonamide (PFOSA) Induces Cardiotoxicity via Aryl Hydrocarbon Receptor Activation in Zebrafish

Chen

Zheng

Yang

et al. 2022

Environ. Sci. Technol.

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“…SOD is an ubiquitous antioxidant enzyme that catalyzes the conversion of superoxide hydrogen ion radical (O2-) to hydrogen peroxide (H2O2) ( Sakamoto and Imai, 2017 ). Excessive accumulation of ROS can lead to a variety of cardiovascular diseases, such as endothelial dysfunction and, atherosclerosis ( Victor et al, 2009 ; Chistiakov et al, 2018 ), and it has been shown that the accumulation of ROS has a toxic effect on the heart development of zebrafish ( Cao et al, 2020 ; Meng et al, 2020 ). Our experimental results showed that with the increase of CsA concentration, the accumulation of ROS in the pericardium of juvenile zebrafish gradually increased and SOD activity gradually decreased, while MDA content significantly increased.…”

Section: Discussionmentioning

confidence: 99%

Cyclosporine A Induces Cardiac Developmental Toxicity in Zebrafish by Up-Regulation of Wnt Signaling and Oxidative Stress

et al. 2021

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Due to the widely application of Cyclosporine A (CsA) as an immunosuppressant in clinic, it is necessary to study its potential toxicity. Therefore, we used zebrafish as a model animal to evaluate the toxicity of CsA on embryonic development. Exposure of zebrafish embryos to CsA at concentrations of 5 mg/L, 10 mg/L, and 15 mg/L from 12 hpf to 72 hpf resulted in abnormal embryonic development, including cardiac malformation, pericardial edema, decreased heart rate, decreased blood flow velocity, deposition at yolk sac, shortened body length, and increased distance between venous sinus and arterial bulb (SV-BA). The expression of genes related to cardiac development was disordered, and the apoptotic genes were up-regulated. Oxidative stress level was up-regulated and accumulated in pericardium in a dose-dependent manner. Astaxanthin (ATX) treatment could significantly alleviate zebrafish heart defects. CsA induced up-regulation of Wnt signaling in zebrafish, and IWR-1, an inhibitor of Wnt signaling pathway, could effectively rescue the heart defects induced by CsA. Together, our study indicated that CsA induced cardiac developmental toxicity in zebrafish larvae through up-regulating oxidative stress and Wnt signaling, contributing to a more comprehensive evaluation of the safety of the drug.

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“…The development of the zebrafish heart is a complex and orderly process 37,38 . In short, during heart development, the myocardial progenitor cells located in the lateral mesoderm gradually converge in the midline of the abdomen and form a linear heart tube.…”

Section: Discussionmentioning

confidence: 99%

“…The development of the zebrafish heart is a complex and orderly process. 37 , 38 In short, during heart development, the myocardial progenitor cells located in the lateral mesoderm gradually converge in the midline of the abdomen and form a linear heart tube. After the proliferation of the cardiomyocytes, the chamber expands continuously accompanied by morphological changes, finally developing the subdivisions of an atrium and a ventricle.…”

Section: Discussionmentioning

confidence: 99%

Nitazoxanide induced myocardial injury in zebrafish embryos by activating oxidative stress response

Gong

Shen

Zhang

et al. 2021

J Cellular Molecular Medi

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Nitazoxanide (NTZ) is a broad‐spectrum antiparasitic and antiviral drug (thiazole). However, although NTZ has been extensively used, there are no reports concerning its toxicology in vertebrates. This study used the zebrafish as a vertebrate model to evaluate the safety of NTZ and to analyse the related molecular mechanisms. The experimental results showed that zebrafish embryos exposed to NTZ had cardiac malformation and dysfunction. NTZ also significantly inhibited proliferation and promoted apoptosis in cardiomyocytes. Transcriptomic analysis used compared gene expression levels between zebrafish embryos in the NTZ treatment and the control groups identified 200 upregulated genes and 232 downregulated genes. Analysis by Kyoto encyclopaedia of genes and genomes (KEGG) and gene ontology (GO) showed that signal pathways on cardiomyocyte development were inhibited while the oxidative stress pathways were activated. Further experiments showed that NTZ increased the content of reactive oxygen species (ROS) in the hearts of zebrafish. Antioxidant gadofullerene nanoparticles (GFNPs) significantly alleviated the developmental toxicity to the heart, indicating that NTZ activated the oxidative stress response to cause embryonic cardiomyocyte injury in zebrafish. This study provides evidence that NTZ causes developmental abnormalities in the cardiovascular system of zebrafish.

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Exposure to pyrimethanil induces developmental toxicity and cardiotoxicity in zebrafish

Cited by 64 publications

References 63 publications

Perfluorooctane Sulfonamide (PFOSA) Induces Cardiotoxicity via Aryl Hydrocarbon Receptor Activation in Zebrafish

Perfluorooctane Sulfonamide (PFOSA) Induces Cardiotoxicity via Aryl Hydrocarbon Receptor Activation in Zebrafish

Cyclosporine A Induces Cardiac Developmental Toxicity in Zebrafish by Up-Regulation of Wnt Signaling and Oxidative Stress

Nitazoxanide induced myocardial injury in zebrafish embryos by activating oxidative stress response

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