2. Academic Validation
  3. Novel insights into DBP-induced zebrafish liver inflammatory damage: Ferroptosis activating the HMGB1-TLR4-NF-κB signaling pathway

Novel insights into DBP-induced zebrafish liver inflammatory damage: Ferroptosis activating the HMGB1-TLR4-NF-κB signaling pathway

  • Environ Pollut. 2025 Jul 1:376:126395. doi: 10.1016/j.envpol.2025.126395.
Zixu Li 1,  Yacan Gong 1,  Emmanuel Sunday Okeke 2,  Dan Li 1,  Yao Chen 3,  Weiwei Feng 3,  Ting Zhao 4,  Liuqing Yang 4,  Guanghua Mao 5,  Xiangyang Wu 6
Affiliations

Affiliations

  • 1 School of the Environment and Safety Engineering Jiangsu University, 301 Xuefu Rd, Zhenjiang, 212013, China.
  • 2 School of the Environment and Safety Engineering Jiangsu University, 301 Xuefu Rd, Zhenjiang, 212013, China; Department of Biochemistry, Faculty of Biological Science & Natural Science Unit, School of General Studies, University of Nigeria, Nsukka, Enugu State, 410001, Nigeria.
  • 3 School of the Environment and Safety Engineering Jiangsu University, 301 Xuefu Rd, Zhenjiang, 212013, China; School of Emergency Management, Jiangsu University, 301 Xuefu Rd, Zhenjiang, 212013, China.
  • 4 School of Chemistry and Chemical Engineering, Jiangsu University, 301 Xuefu Rd, Zhenjiang, 212013, China.
  • 5 School of the Environment and Safety Engineering Jiangsu University, 301 Xuefu Rd, Zhenjiang, 212013, China. Electronic address: maoyun82@sina.com.
  • 6 School of the Environment and Safety Engineering Jiangsu University, 301 Xuefu Rd, Zhenjiang, 212013, China. Electronic address: wuxy@ujs.edu.cn.
PMID: 40345373 DOI: 10.1016/j.envpol.2025.126395
Abstract

Typical plasticizer dibutyl phthalate (DBP) has been demonstrated to induce hepatotoxicity in zebrafish, but the underlying molecular mechanisms remain incompletely elucidated. Numerous studies have shown that Ferroptosis is involved in the pathophysiological progression of hepatic disease. However, it remains unclear whether Ferroptosis is involved in the DBP-induced hepatotoxicity in zebrafish. Initially, histopathological analyses have preliminarily confirmed that DBP can activate inflammatory responses in the zebrafish liver. Further investigation revealed that DBP induces Ferroptosis in the zebrafish liver, characterized by iron overload, lipid peroxidation, and aberrant activation of Ferroptosis pathways. Furthermore, DBP exposure induced Ferroptosis, disrupting cell membranes and subsequent release of HMGB1, which are sensed by immunocytes TLR4/NF-κB signaling pathways, thereby activating the innate immune response in a context-dependent manner. Moreover, the Ferroptosis inhibitor Fer-1 effectively rescues the activation of HMGB1-TLR4/NF-κB-mediated immune processes. Overall, this work enriches the molecular mechanism of DBP-induced zebrafish liver inflammatory damage and provides a reliable biomarker for future environmental risk assessment of DBP.

Keywords

Dibutyl phthalate; Ferroptosis; HMGB1-TLR4/NF-κB; Inflammatory damage; Zebrafish.

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