2. Academic Validation
  3. Perfluorooctanoic acid (PFOA) exposure induced ferroptosis through the PPARα/FABP7 signaling pathway in the liver of spotted sea bass (Lateolabrax maculatus)

Perfluorooctanoic acid (PFOA) exposure induced ferroptosis through the PPARα/FABP7 signaling pathway in the liver of spotted sea bass (Lateolabrax maculatus)

  • Fish Shellfish Immunol. 2025 Oct 8:168:110908. doi: 10.1016/j.fsi.2025.110908.
Jieyun Guo 1,  Lulu Yan 2,  Chao Zhao 2,  Bo Zhang 2,  Lihua Qiu 3,  Shengkang Li 4
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Marine Biology, Shantou University, Shantou, 515063, China; State Key Laboratory of Mariculture Biobreeding and Sustainable Goods (BRESG), Guangdong Provincial Key Laboratory of Fishery Ecology and Environment, Key Laboratory of South China Sea Fishery Resources Exploitation & Utilization, Ministry of Agriculture and Rural Affairs, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, 510300, China.
  • 2 State Key Laboratory of Mariculture Biobreeding and Sustainable Goods (BRESG), Guangdong Provincial Key Laboratory of Fishery Ecology and Environment, Key Laboratory of South China Sea Fishery Resources Exploitation & Utilization, Ministry of Agriculture and Rural Affairs, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, 510300, China.
  • 3 State Key Laboratory of Mariculture Biobreeding and Sustainable Goods (BRESG), Guangdong Provincial Key Laboratory of Fishery Ecology and Environment, Key Laboratory of South China Sea Fishery Resources Exploitation & Utilization, Ministry of Agriculture and Rural Affairs, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, 510300, China. Electronic address: [email protected].
  • 4 Guangdong Provincial Key Laboratory of Marine Biology, Shantou University, Shantou, 515063, China. Electronic address: [email protected].
PMID: 41067592 DOI: 10.1016/j.fsi.2025.110908
Abstract

Perfluorooctanoic acid (PFOA) poses a significant threat to ecological environments and human health due to its persistence, bioaccumulation, and toxicity. While the hepatotoxic effects of PFOA have been explored in humans and non-humans, its molecular mechanisms in marine teleosts remain unclear. To investigate the effects of PFOA on fish liver, both in vitro and in vivo experiments were conducted. In vivo, spotted sea bass were exposed to different concentrations of PFOA for 14 days. H&E staining revealed significant liver damage at high PFOA concentrations. RNA Sequencing indicated that PFOA activated the Ferroptosis pathway in the liver. In liver tissue, PFOA exposure led to reduced GPX4 activity, increased Fe2+levels and lipid peroxidation. These findings were also observed in vitro, where PFOA exposure significantly inhibited the viability of spotted sea bass liver cells (LML cells), promoted ROS accumulation, and increased lipid peroxidation. Notably, mitochondrial damage and elevated Fe2+levels were also observed in LML cells. Ferrostatin-1, Ferroptosis inhibitor, alleviated lipid peroxidation and restored cell viability, confirming the role of Ferroptosis in PFOA-induced toxicity. Additionally, our study identified that PFOA promotes cellular fatty acid accumulation, lipid peroxidation, and Ferroptosis by activating the PPARα signaling pathway. This activation upregulated the expression of fatty acid binding protein 7 (FABP7), a downstream target of PPARα. Knockdown FABP7 rescued PFOA-induced Ferroptosis. This study revealed for the first time that PFOA induces liver damage by triggering Ferroptosis in teleosts. This result provides new insights into the molecular mechanisms of PFOA hepatotoxicity in marine fish.

Keywords

FABP7; Ferroptosis; Liver; PFOA; PPARα; Spotted sea bass cells.

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