Integrated Network toxicology and Transcriptomics Uncover that the Involvement of NF-κB/NLRP3 Pyroptosis Axis in Mediating BaP-Induced Hepatotoxicity and Fibrosis.

Authors

Bohe Wang, Xiuxia Dong, Jiayue Li, Xiaojuan Feng, Yongkang Chen, Na Liu, Pengjuan Fu, Junling Wang, Xiangli Li

Published in

Environmental toxicology and pharmacology. Pages 105179. Sep 26, 2026. Epub Sep 26, 2026.

Abstract

Benzo[a]pyrene (BaP), a ubiquitous environmental pollutant, exerts hepatotoxicity primarily through its metabolite BPDE. This study combined network toxicology and experimental validation to delineate the mechanisms of BaP-induced liver injury and fibrosis. Network analysis identified ICAM-1 as a potential core target, and previous clinical data confirmed its upregulation in liver injury patients. In a rat model, BaP exposure induced dose-dependent hepatic injury and oxidative stress. Mechanistically, BaP activated the NF-κB/TNF-α signaling axis, upregulating ICAM-1 and initiating NLRP3 inflammasome assembly. Activated NLRP3 promoted Caspase-1-dependent cleavage of GSDMD, leading to hepatocyte pyroptosis and the release of IL-1β and IL-18. Concurrently, ICAM-1 facilitated inflammatory cell infiltration. This sustained inflammatory microenvironment ultimately activated the TGF-β/α-SMA/Col-I axis, driving hepatic stellate cell activation and excessive extracellular matrix deposition, thereby promoting liver fibrosis. Our findings elucidate a cascading pathway linking BaP exposure to oxidative stress, NLRP3-mediated pyroptosis, and hepatic fibrogenesis.

PMID:
42800691
Bibliographic data and abstract were imported from PubMed on 27 Sep 2026.

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