Zou Hui, Tan Yumei, Ren Xiyi, Li Zhu, Liu Yongxiang
Key Laboratory of Plant Resource Conservation and Germplasm Innovation in Mountainous Region (Ministry of Education), Collaborative Innovation Center for Mountain Ecology and Agro-Bioengineering (CICMEAB), College of Life Sciences/Institute of Agro-Bioengineering, Guizhou University, Guiyang 550025, China.
Guizhou Key Laboratory of Agricultural Microbiology, Guizhou Academy of Agricultural Sciences, Guiyang 550009, China.
Toxics. 2025 Jun 6;13(6):480. doi: 10.3390/toxics13060480.
P-phenylenediamines (PPDs) and their quinone derivatives (PPDQs), emerging pollutants widespread in urban environments, exhibit biotoxicological risks. Epidemiological studies suggest their adverse impacts on intestinal health, yet the underlying mechanisms remain unclear. This study aimed to investigate the potential mechanisms of enterotoxicity induced by 13 PPDs and PPDQs using network toxicology and molecular docking approaches. Through the SuperPred, STITCH, GeneCards, and OMIM databases, 182 potential targets associated with PPD- and PPDQ-induced enterotoxicity were identified. Thirty hub targets, including SRC, EGFR, CASP3, and others, were prioritized using STRING and Cytoscape tools. GO and KEGG enrichment analyses via the DAVID and FUMA databases revealed significant enrichment of core enterotoxicity-related targets in the MAPK signaling pathway and the calcium signaling pathway. Molecular docking with AutoDock confirmed strong binding affinities between PPDs/PPDQs and core targets. These results suggest that PPDs and PPDQs may promote the onset and progression of bowel cancer and intestinal inflammation by modulating cancer cell death, proliferation, and inflammatory signaling pathways. This research provides a theoretical framework for elucidating the molecular mechanisms of PPD- and PPDQ-induced enterotoxicity, offering insights for the prevention of associated diseases.
对苯二胺（PPDs）及其醌衍生物（PPDQs）是城市环境中广泛存在的新兴污染物，具有生物毒理学风险。流行病学研究表明它们对肠道健康有不利影响，但其潜在机制仍不清楚。本研究旨在使用网络毒理学和分子对接方法，研究13种PPDs和PPDQs诱导肠毒性的潜在机制。通过SuperPred、STITCH、GeneCards和OMIM数据库，确定了182个与PPD和PPDQ诱导的肠毒性相关的潜在靶点。使用STRING和Cytoscape工具对包括SRC、EGFR、CASP3等在内的30个核心靶点进行了优先级排序。通过DAVID和FUMA数据库进行的GO和KEGG富集分析显示，核心肠毒性相关靶点在MAPK信号通路和钙信号通路中显著富集。使用AutoDock进行的分子对接证实了PPDs/PPDQs与核心靶点之间具有很强的结合亲和力。这些结果表明，PPDs和PPDQs可能通过调节癌细胞死亡、增殖和炎症信号通路，促进肠癌和肠道炎症的发生和发展。本研究为阐明PPD和PPDQ诱导肠毒性的分子机制提供了理论框架，为预防相关疾病提供了见解。
