Metformin-Induced Epigenetic Toxicity in Zebrafish: Experimental and Molecular Dynamics Simulation Studies

Lin, Wenting; Yan, Yuanyang; Ping, Senwen; Li, Ping; Li, Diandi; Hu, Junjie; Liu, Wei; Wen, Xiufang; Ren, Yuan

doi:10.1021/acs.est.0c06052

Cited by 38 publications

(15 citation statements)

References 46 publications

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“…Low-dose metformin exposure for a long time could cause a significant upregulation of numerous endocrine-related genes in FHM [ 28 ]. Metformin affected the expression of genes related to neurological and cardiovascular development and the expression of CYP3A65, GSTM1, p53, and DNMT1 genes in the liver in zebrafish [ 29 , 30 ]. It was also found that metformin could induce oxidative stress and the two-generation endocrine disruption in Oryzias latipes [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Genotoxicity Evaluation of Metformin in Freshwater Planarian Dugesia japonica by the Comet Assay and RAPD Analysis

Yin

Feng

et al. 2022

BioMed Research International

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Objective. To investigate the genotoxicity of metformin on planarian with different concentrations and exposure times. Methods. The planarians were treated, respectively, with 10 mmol/L and 50 mmol/L metformin for 1, 3, and 5 days, and then, the comet assay and random amplified polymorphic DNA (RAPD) analysis were performed. 13 random primers were used for PCR amplification with the genomic DNAs as templates. Planarians cultured in clear water were used as the control. Genomic template stability (GTS) was calculated by comparing and analyzing the RAPD patterns of the control group and the treatment groups. Results. In the comet assay, DNA damage of planarians treated with 10 mmol/L metformin for 1, 3, and 5 days was 10.2%, 25.4%, and 36.8%, respectively, and that of planarians treated with 50 mmol/L metformin was 40.6%, 62.8%, and 65.4%, respectively. GTS values of planarians exposed to 10 mmol/L metformin for 1, 3, and 5 days were 64.1%, 62.8%, and 52.6%, respectively, and those of planarians exposed to 50 mmol/L metformin for 1, 3, and 5 days were 52.6%, 51.3%, and 50%, respectively. DNA damage increased and GTS values decreased with the increasing metformin exposure concentration and exposure time. Conclusion. Metformin has certain genotoxicity on planarian in a dose- and time-related manner. The comet assay and RAPD analysis are highly sensitive methods for detecting genotoxicity with drugs.

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Section: Discussionmentioning

confidence: 99%

Genotoxicity Evaluation of Metformin in Freshwater Planarian Dugesia japonica by the Comet Assay and RAPD Analysis

Yin

Feng

et al. 2022

BioMed Research International

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“… 78 Furthermore, it was found to accumulate in the liver, causing toxicity after prolonged aquatic exposure in adult zebrafish. 79 …”

Section: Resultsmentioning

confidence: 99%

Graphene-based phenformin carriers for cancer cell treatment: a comparative study between oxidized and pegylated pristine graphene in human cells and zebrafish

et al. 2022

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“…Many studies , have demonstrated the success of the MM/PBSA method for estimating the binding free energies of small molecules to macromolecules. Before calculating the binding free energies, we first analyzed the dynamic stability of the two IL/AChE complexes through an RMSD (root-mean-square deviation) analysis.…”

Section: Results and Discussionmentioning

confidence: 99%

Comprehensive Interrogation on Acetylcholinesterase Inhibition by Ionic Liquids Using Machine Learning and Molecular Modeling

Yan

et al. 2021

Environ. Sci. Technol.

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Quantitative structure−activity relationship (QSAR) modeling can be used to predict the toxicity of ionic liquids (ILs), but most QSAR models have been constructed by arbitrarily selecting one machine learning method and ignored the overall interactions between ILs and biological systems, such as proteins. In order to obtain more reliable and interpretable QSAR models and reveal the related molecular mechanism, we performed a systematic analysis of acetylcholinesterase (AChE) inhibition by 153 ILs using machine learning and molecular modeling. Our results showed that more reliable and stable QSAR models (R 2 > 0.85 for both cross-validation and external validation) were obtained by combining the results from multiple machine learning approaches. In addition, molecular docking results revealed that the cations and organic anions of ILs bound to specific amino acid residues of AChE through noncovalent interactions such as π interactions and hydrogen bonds. The calculation results of binding free energy showed that an electrostatic interaction (ΔE ele < −285 kJ/ mol) was the main driving force for the binding of ILs to AChE. The overall findings from this investigation demonstrate that a systematic approach is much more convincing. Future research in this direction will help design the next generation of biosafe ILs.

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Metformin-Induced Epigenetic Toxicity in Zebrafish: Experimental and Molecular Dynamics Simulation Studies

Cited by 38 publications

References 46 publications

Genotoxicity Evaluation of Metformin in Freshwater Planarian Dugesia japonica by the Comet Assay and RAPD Analysis

Genotoxicity Evaluation of Metformin in Freshwater Planarian Dugesia japonica by the Comet Assay and RAPD Analysis

Graphene-based phenformin carriers for cancer cell treatment: a comparative study between oxidized and pegylated pristine graphene in human cells and zebrafish

Comprehensive Interrogation on Acetylcholinesterase Inhibition by Ionic Liquids Using Machine Learning and Molecular Modeling

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