• Medicine · Oct 2024

    Network toxicology and molecular docking to investigative the non-acetylcholinesterase mechanisms and targets of cardiotoxicity injury induced by organophosphorus pesticides.

    • Yongmei Guo and Nan Li.
    • Jiangxi Medical College, Shangrao, Jiangxi, China.
    • Medicine (Baltimore). 2024 Oct 11; 103 (41): e39963e39963.

    BackgroundOrganophosphorus pesticides (OPPs) are widely used in the world, however, OPP poisoning often occurs because of improper use and lack of protective measures. Cardiotoxicity injury induced by OPPs is insidious, and it does not receive attention until the end stage of OPP poisoning. Heart failure or arrhythmia gradually becomes the main lethal cause of OPP poisoning patients.MethodsIn this study, network toxicology and molecular docking were employed to investigate the non-acetylcholinesterase targets and mechanisms of cardiotoxicity injury induced by OPPs.ResultsOne hundred twenty-three targets of dichlorvos, 205 targets of methidathion, and 337 targets of malathion were searched from SwissTargetPreict, STITCH and PharmMapper database. Additionally, 1379 targets related to cardiotoxicity injury were acquired from GeneCards and OMIM database. Ninety-six mutual targets between OPPs and cardiotoxicity injury were considered as the potential cardiotoxicity injury targets induced by OPPs. The protein-protein interaction (PPI) network was constructed using STING database, and 21 core targets were identified by Cytoscape software, such as AKT1, ESR1, HSP90AA1, MAPK1, MMP9, and MAPK8. Gene ontology and KEGG enrichment analysis revealed that cell migration, apoptotic process, protein phosphorylation and signal transduction were the major biological functions associated with OPPs-induced cardiotoxicity injury, and OPPs-induced cardiotoxicity injury might be regulated by MAPK, PI3K-Akt, VEGF signaling pathway. Docking results manifested that the best binding target for dichlorvos, methidathion and malathion were MAPK9 (-7.1 kcal/mol), MAPK1 (-8.1 kcal/mol) and HSP90AA1 (-8.6 kcal/mol) with the lowest affinity, respectively.ConclusionThe core targets and non-AchE mechanisms were explored by network toxicology and molecular docking, providing a theoretical basis for the treatment of OPP-induced cardiotoxicity injury.Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.

      Pubmed     Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…