Investigation of the Toxicity and Mechanisms of Acetyl Tributyl Citrate in Chronic Liver Injury Using Network Toxicology and Molecular Docking Techniques

Yulong Wang; Wanjie Gu

doi:10.54097/b39h2z79

Authors

Yulong Wang
Wanjie Gu

DOI:

https://doi.org/10.54097/b39h2z79

Keywords:

Acetyl Tributyl Citrate (ATBC), Network Toxicology, Liver Injury, Molecular Docking

Abstract

Acetyl tributyl citrate (ATBC) is a commonly used plasticizing agent. Recent studies have shown that long-term exposure to ATBC may cause liver injury, but the mechanism of injury still needs to be further studied. The aim of this study is to investigate the hepatotoxicity and potential mechanism of ATBC using network toxicology strategy. Two online sites, ADMETlab and ProTex, were used to search the toxic effects of acetyl-tributyl citrate. Then six databases, ChEMBL, STITCH, SwissTargetPrediction, GeneCards, TTD, OMIM, were used to search the toxic effects of acetyl-tributyl citrate. We identified 43 potential biomarkers associated with ATBC exposure and liver injury. Using comprehensive analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we found that the targets of ATBC induced liver injury were mainly enriched in metabolic disorders, oxidative stress, inflammatory response, organelle dysfunction, abnormal enzyme activity, and protein kinase signaling pathway disorders. Then we used Cytoscape software and STRING website optimization to highlight five core targets. Finally, we used molecular docking technology to combine these five core targets, and confirmed the high binding affinity of ATBC with the core targets. In summary, these results suggest that ATBC may induce liver injury through a closely related cascade of metabolism imbalance, organelle dysfunction, oxidative stress, inflammation, and fibrosis. On the basis of previous findings, this study confirmed that ATBC causes chronic liver injury, explored its injury mechanism, and provided a systematic and effective framework for researchers to evaluate the potential toxicity of various chemical products and medical devices.

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