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Analyzing the potential targets and mechanisms of liver damage induced by acetyl tributyl citrate plasticizer using
Dong-Qun Guo1, Yu-Ming Fang2, Zhen-Dong Sun2
1Department of Urology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Background:
Acetyl tributyl citrate (ATBC) may have adverse effects on liver health; however, the underlying mechanisms and pathophysiology remain unclear. The objective of this study was to elucidate the complex effects of ATBC on the liver and to determine the underlying molecular mechanisms by which environmental pollutants affect the disease process.
Methods:
We used network toxicology and molecular docking techniques to analyze potential targets and mechanisms of liver injury caused by ATBC plasticizer. Potential targets associated with ATBC exposure and liver injury were identified by using ChEMBL, STITCH, GeneCards and OMIM databases. Enrichment analysis was performed using the DAVID database (https://david.ncifcrf.gov/) to identify biological pathways associated with these genes. Finally, transcription quantitative polymerase chain reaction, CCK-8 assay, Western blot, and immunofluorescence staining were used to assess the effect of candidate potential targets on liver injury.
Results:
A total of 74 common targets associated with ATBC and liver injury were obtained. Enrichment analysis emphasized the association between these plastocyanin-targeted genes and the apoptotic pathway, suggesting that plastocyanin has a broad impact on cell survival. Moreover, molecular docking analysis demonstrated that ATBC exhibited a specific binding affinity for TNF-α, thereby suggesting that TNF-α plays a pivotal role in the regulation of liver damage pathogenesis. In vitro experiments further validated the expression of this molecule with the apoptosis marker molecules BAX and Bcl2 in ATBC-induced liver injury.
Conclusion:
The study suggests that TNF-α is involved in the process of ATBC-induced liver damage and may be related to cell apoptosis.
Insights
Acetyl tributyl citrate (ATBC) may harm liver health. This study found ATBC plasticizer induces liver injury by affecting cell apoptosis, with TNF-α playing a key role in the damage process.
Area of Science:
- Toxicology
- Molecular Biology
- Environmental Health
Background:
- Acetyl tributyl citrate (ATBC) is a plasticizer with potential adverse effects on liver health.
- The precise mechanisms and pathophysiology of ATBC-induced liver injury are not well understood.
- Investigating environmental pollutants' impact on disease processes is crucial for public health.
Purpose of the Study:
- To elucidate the complex effects of ATBC on liver health.
- To identify the molecular mechanisms underlying ATBC-induced liver injury.
- To determine the role of specific molecular targets in the disease process.
Main Methods:
- Network toxicology and molecular docking were employed to identify potential ATBC targets.
- Databases like ChEMBL, STITCH, GeneCards, and OMIM were used for target identification.
- In vitro methods including qPCR, CCK-8 assay, Western blot, and immunofluorescence validated candidate targets.
Main Results:
- 74 common targets associated with ATBC and liver injury were identified.
- Enrichment analysis indicated a link between these targets and the apoptotic pathway.
- Molecular docking revealed ATBC binds to TNF-α, which was further validated in vitro with apoptosis markers BAX and Bcl2.
Conclusions:
- Tumor Necrosis Factor-alpha (TNF-α) is implicated in ATBC-induced liver damage.
- The liver injury caused by ATBC appears to be associated with cellular apoptosis.
- Understanding these mechanisms can inform strategies for mitigating plasticizer-related health risks.
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