Guo Dong-Qun, Fang Yu-Ming, Sun Zhen-Dong, Zeng Ya-Fen, Wang Gui-Dan, Liang Jin-Wei
Department of Urology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Department of Anesthesiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Front Pharmacol. 2025 Jul 16;16:1636576. doi: 10.3389/fphar.2025.1636576. eCollection 2025.
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.
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.
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. experiments further validated the expression of this molecule with the apoptosis marker molecules BAX and Bcl2 in ATBC-induced liver injury.
The study suggests that TNF-α is involved in the process of ATBC-induced liver damage and may be related to cell apoptosis.
乙酰柠檬酸三丁酯（ATBC）可能对肝脏健康产生不利影响；然而，其潜在机制和病理生理学仍不清楚。本研究的目的是阐明ATBC对肝脏的复杂影响，并确定环境污染物影响疾病进程的潜在分子机制。
我们使用网络毒理学和分子对接技术分析由ATBC增塑剂引起的肝损伤的潜在靶点和机制。通过使用ChEMBL、STITCH、GeneCards和OMIM数据库鉴定与ATBC暴露和肝损伤相关的潜在靶点。使用DAVID数据库（https://david.ncifcrf.gov/）进行富集分析，以鉴定与这些基因相关的生物学途径。最后，采用转录定量聚合酶链反应、CCK-8测定、蛋白质印迹和免疫荧光染色来评估候选潜在靶点对肝损伤的影响。
共获得74个与ATBC和肝损伤相关的共同靶点。富集分析强调了这些质体蓝素靶向基因与凋亡途径之间的关联，表明质体蓝素对细胞存活具有广泛影响。此外，分子对接分析表明，ATBC对TNF-α表现出特异性结合亲和力，从而表明TNF-α在肝损伤发病机制的调节中起关键作用。实验进一步验证了该分子与ATBC诱导的肝损伤中凋亡标记分子BAX和Bcl2的表达。
该研究表明TNF-α参与ATBC诱导的肝损伤过程，可能与细胞凋亡有关。
