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  3. Glycidol induces necroptosis and inflammation through autophagy-necrosome pathway in renal cell and mice

Glycidol induces necroptosis and inflammation through autophagy-necrosome pathway in renal cell and mice

  • Sci Total Environ. 2025 Mar 10:968:178852. doi: 10.1016/j.scitotenv.2025.178852.
Jing Lu 1,  Hongdi Wei 1,  Xinyu Yao 1,  Yuelin Chen 1,  Meitong Liu 1,  Shuang Guan 2
Affiliations

Affiliations

  • 1 Department of Food Quality and Safety, College of Food Science and Engineering, Jilin University, Changchun, Jilin 130062, PR China.
  • 2 Department of Food Quality and Safety, College of Food Science and Engineering, Jilin University, Changchun, Jilin 130062, PR China; Key Laboratory of Zoonosis, Ministry of Education College of Veterinary Medicine, Jilin University, Changchun, Jilin 130062, PR China. Electronic address: guan_shuang22@jlu.edu.cn.
PMID: 39965374 DOI: 10.1016/j.scitotenv.2025.178852
Abstract

Glycidol is a common food contaminant, and its main target organ is the kidney. However, the mechanism of nephrotoxicity of glycidol has not been fully elucidated. In this paper, we investigated the mechanism of glycidol toxicity in mice kidneys and NRK-52E cells. We found that glycidol exposure induced Necroptosis in renal cells through the RIPK1/RIPK3/MLKL pathway. Mechanistically, it was further found that glycidol blocked renal cell Autophagy and induced ectopic aggregation of p62. Accumulated p62 recruited RIPK1 and activated downstream RIPK1/RIPK3/MLKL necrosome production. At the same time, the accumulated p62 could also participate in the activation of intracellular NF-κB nuclear transcription factor by interacting with RIPK1 to form a signalling complex, which promoted the secretion of inflammatory factors TNF-α and IL-1β, and induced inflammation in the kidney. Our present study provided a new understanding of the complex mechanism of glycidol on renal injury.

Keywords

Glycidol; Inflammation; NF-κB; Necroptosis; p62.

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