2. Academic Validation
  3. Naringenin alleviates endotoxin-induced acute kidney injury in chicken by inhibiting pyroptosis through PINK1-dependent mitophagy

Naringenin alleviates endotoxin-induced acute kidney injury in chicken by inhibiting pyroptosis through PINK1-dependent mitophagy

  • Phytomedicine. 2025 Dec:149:157429. doi: 10.1016/j.phymed.2025.157429.
Xuewei Chen 1,  Xu Shi 1,  Xuejiao Yang 1,  Meichen Gao 1,  Tong Nie 1,  Shiwen Xu 2
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
  • 2 College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China; Laboratory of Embryo Biotechnology, College of Life Science, Northeast Agricultural University, Harbin 150030, China. Electronic address: [email protected].
PMID: 41297318 DOI: 10.1016/j.phymed.2025.157429
Abstract

Background: Lipopolysaccharide (LPS), known as endotoxin, constitutes a major component of the cell wall of Gram-negative bacteria and threatens public health. Naringenin (Nar), as a phenolic compound, has antioxidant, anti-inflammatory, and anti-bacterial function. Nevertheless, the mechanism of LPS-induced nephrotoxicity in poultry and the protective effect of Nar warrant further exploration.

Methods: Based on the LPS or/and Nar exposure models, the study explored the damaged mechanism of LPS-induced acute kidney injury (AKI) and the antagonistic effect of Nar through Western blot, Immunofluorescence, and Molecular docking analysis, and so on.

Results: The results showed that Nar alleviated LPS exposure-elicited kidney structural damage and oxidative damage. Further analysis revealed that LPS exposure promoted mitochondrial cristae fragmentation, decreased mitochondrial membrane potential (MMP) and mitochondrial electron transport chain (ETC) complex protein expression, induced mitochondrial-ROS (mito-ROS) accumulation, downregulated mitophagy-related proteins expression, and upregulated pyroptosis-related proteins expression in kidney. Nar mitigated these injuries caused by LPS in vivo and in vitro. Molecular docking and dynamics and Cell thermal shift assay analysis further indicated that Nar directly bound to PINK1 and promoted the protein stability. The addition of Rotenone, chloroquine (CQ) or si-PINK1 demonstrated that Nar alleviated LPS-induced nephrotoxicity by promoting Mitophagy to reduce ROS/TXNIP/NLRP3-driven Pyroptosis.

Conclusion: This study demonstrated that Nar targeted PINK1-dependent Mitophagy to alleviate ROS/TXNIP/NLRP3-driven Pyroptosis, thereby mitigating AKI in chickens. The study provided a theoretical and experimental basis for LPS-induced AKI and demonstrated that Nar could reduce LPS-induced nephrotoxicity, thereby offering a reference for comparative medicine.

Keywords

Acute kidney injury; Lipopolysaccharide; Mitochondria damage; Naringenin; PINK1-dependent mitophagy; Pyroptosis.

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