Carboxin can induce cardiotoxicity in zebrafish embryos

Huang, Yong; Wang, Ziqin; Peng, Yuyang; Xu, Ran; Yan, Jiajie; Xiong, Cong; Ma, Jinze; Zhong, Keyuan; Lu, Huiqiang

doi:10.1016/j.ecoenv.2022.113318

Cited by 17 publications

(18 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, one must keep in mind that besides gata4 , acute exposure to p-TSA also caused abnormalities in the expression of another tested cardiac gene, which was vmhc . This gene is initially expressed in the anterolateral mesoderm and subsequently, its expression is restricted to the cardiac ventricle [ 92 ]. However, the slight alterations in its expression level observed in the study seemed not sufficient to cause noticeable cardiotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Toxicity Assessment of an Anti-Cancer Drug of p-Toluene Sulfonamide in Zebrafish Larvae Based on Cardiovascular and Locomotion Activities

et al. 2022

View full text Add to dashboard Cite

p-toluene sulfonamide (p-TSA), a small molecular drug with antineoplastic activity is widely gaining interest from researchers because of its pharmacological activities. In this study, we explored the potential cardio and neural toxicity of p-TSA in sublethal concentrations by using zebrafish as an in vivo animal model. Based on the acute toxicity assay, the 96hr LC50 was estimated as 204.3 ppm, suggesting the overall toxicity of p-TSA is relatively low in zebrafish larvae. For the cardiotoxicity test, we found that p-TSA caused only a minor alteration in treated larvae after no overall significant alterations were observed in cardiac rhythm and cardiac physiology parameters, as supported by the results from expression level measurements of several cardiac development marker genes. On the other hand, we found that acute p-TSA exposure significantly increased the larval locomotion activity during the photomotor test while prolonged exposure (4 days) reduced the locomotor startle reflex activities in zebrafish. In addition, a higher respiratory rate and blood flow velocity was also observed in the acutely treated fish groups compared to the untreated group. Finally, by molecular docking, we found that p-TSA has a moderate binding affinity to skeletal muscle myosin II subfragment 1 (S1), ATPase activity, actin- and Ca2+-stimulated myosin S1 ATPase, and v-type proton ATPase. These binding interactions between p-TSA and proteins offer insights into the potential molecular mechanism of action of p-TSA on observed altered responses toward photo and vibration stimuli and minor altered vascular performance in the zebrafish larvae.

show abstract

Section: Discussionmentioning

confidence: 99%

Toxicity Assessment of an Anti-Cancer Drug of p-Toluene Sulfonamide in Zebrafish Larvae Based on Cardiovascular and Locomotion Activities

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The melting points of all synthesized chemicals were measured by an XT-4 micro melting point instrument. 1 H NMR and 13 C NMR spectra of all compounds were acquired by a Bruker Advance neo spectrometer (400 MHz). Chemical shifts (δ values) were reported in ppm, and coupling constants (J values) were presented in Hz.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…The structures of all prepared diarylhydrazides were identified by HRMS, 1 H NMR, and 13 C NMR spectra. Because of the similarity of their structures, all compounds (1a−1r, 2a−2r, 3a−3h, and 4) showed similar spectroscopic features as expected.…”

Section: Quantitative Proteomic Analysis Protein Extraction Andmentioning

confidence: 99%

“…For this pathway, a total of 31 proteins are involved, 29 of which are differentially downregulated proteins. This leads to the disruption of the ribosome biosynthesis process and impaired ribosome function, which in turn affect the metabolism of amino acids and protein In conclusion, aiming to discover and develop low-cost and versatile antifungal agents, a series of diarylhydrazide compounds (45 examples) were well-designed and prepared, and their structures were characterized by 1 H NMR, 13 C NMR, and HRMS. The results of in vitro bioassay suggested that all compounds displayed definite inhibition activities for the eight strains of phytopathogenic fungi.…”

Section: Effects On Mitochondrial Membrane Potential (Mmp)mentioning

confidence: 99%

“…The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.jafc.2c08027. Synthesis of the control molecules; characterizations of target compounds; 1 H NMR and 13 C NMR spectra of target compounds; HRMS spectra of target compounds; toxicity regression equations of target compounds against phytopathogenic fungi; antifungal activity in vivo of compound 2c against A. solani in tomato; the effect of 2c on the germination of bean seeds; inhibitory rate of compounds on the proliferation of HL-7702 normal hepatocytes; calculated molecular physicochem-ical properties of some potential compounds; basic statistical table of MS results; overview of the detailed information of 1236 differential expression proteins triggered by 2c; GO annotation classification of 1236 differentially expressed proteins by up-and downregulation; COG functional classification chart for the differentially expressed proteins; and KEGG pathway enrichment bubble plot of differentially expressed proteins (PDF)…”

Section: * Sı Supporting Informationmentioning

confidence: 99%

See 2 more Smart Citations

Synthesis, Structure–Activity Relationship, and Mechanism of a Series of Diarylhydrazide Compounds as Potential Antifungal Agents

Liu

et al. 2023

J. Agric. Food Chem.

View full text Add to dashboard Cite

A series of simple diarylhydrazide derivatives (45 examples) were well-designed, prepared, and screened for their antifungal activities both in vitro and in vivo. Bioassay results suggested that all designed compounds had significant activity against Alternaria brassicae (EC 50 = 0.30−8.35 μg/mL). Among of them, 2c, as the highest activity compound, could effectively inhibit the growth of plant pathogens Pyricularia oryza, Fusarium solani, Alternaria solani, Alternaria brassicae, and Alternaria alternate and was more potent than carbendazim and thiabendazole. 2c showed almost 100% protection at 200 μg/mL in vivo activity against A. solani in tomato. Moreover, 2c did not affect the germination of cowpea seed and the growth of normal human hepatocytes. The preliminary mechanistic exploration documented that 2c could result in the abnormal morphology and irregular structure of the cell membrane, destroy the function of mitochondria, increase the reactive oxygen species, and inhibit the proliferation of hypha cell. The above results manifested that target compound 2c could be a potential fungicidal candidate against phytopathogenic diseases for its excellent fungicidal activities.

show abstract

Oxidative stress contributes to flumioxazin‐induced cardiotoxicity in zebrafish embryos

Ma,

Jiang,

Huang

et al. 2023

Enviro Toxic and Chemistry

Self Cite

View full text Add to dashboard Cite

Flumioxazin is a widely applicated herbicide in the control of aquatic plants. Current evidence suggested that flumioxazin could induce cardiac defects (ventricular septal defects) in vertebrates, but the underlining mechanisms remain unclear. Because of the inhibitory effect of flumioxazin on polyphenol oxidase (PPO), the assumption is made that flumioxazin‐induced cardiotoxicity is caused by oxidative stress. The results show that flumioxazin induced cardiac malformations and abnormal gene expression associated with cardiac development. Cardiac malformations include pericardium edema, cardiac linearization, elongated heart, cardiomegaly, cardiac wall hypocellularity, myocardial cell atrophy into granular, and a significant gap between the myocardial intima and the adventitia. An increase in oxidative stress and apoptosis was observed in the cardiac region of zebrafish after exposure to flumioxazin. Antioxidant astaxanthin reversed the cardiac malformations, excessive ROS production and expression of genes for cardiac developmental and apoptosis regulation induced by flumioxazin. In addition, flumioxazin also activated AHR signaling pathway genes (ahr2, cyp1a1, and cyp1b1) and increased porphyrins concentration. In conclusion, the results suggest that excessive ROS production, which could be mediated through AHR, led to apoptosis, contributing to the cardiotoxicity of flumioxazin in zebrafish embryos.

show abstract

Carboxin can induce cardiotoxicity in zebrafish embryos

Cited by 17 publications

References 40 publications

Toxicity Assessment of an Anti-Cancer Drug of p-Toluene Sulfonamide in Zebrafish Larvae Based on Cardiovascular and Locomotion Activities

Toxicity Assessment of an Anti-Cancer Drug of p-Toluene Sulfonamide in Zebrafish Larvae Based on Cardiovascular and Locomotion Activities

Synthesis, Structure–Activity Relationship, and Mechanism of a Series of Diarylhydrazide Compounds as Potential Antifungal Agents

Oxidative stress contributes to flumioxazin‐induced cardiotoxicity in zebrafish embryos

Contact Info

Product

Resources

About