Lycopene mitigates T-2 toxin-induced hepatic ferroptosis by targeting the Nrf2/mitophagy axis in mice

  • NPJ Sci Food. 2026 Feb 7;10(1):94. doi: 10.1038/s41538-026-00736-4.
Xu Yang  #  1 ,  Wenxi Song  #  1 ,  Zhi Lu  #  2  3 ,  Yunhe Chen  1 ,  Youshuang Wang  1 ,  Tingyu Huang  1 ,  Yu Liu  1 ,  Yiming Wang  1 ,  Shuai Chen  4 ,  Yanfei Li  5 ,  Xuebing Wang  1 ,  Cong Zhang  6
Affiliations
  • 1. College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan, China.
  • 2. Department of Psychological and Cognitive Sciences, Tsinghua University, Beijing, China.
  • 3. Institute for Brain and Cognitive Sciences, Tsinghua University, Beijing, China.
  • 4. Department of Gastroenterology and Hepatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
  • 5. Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin, China.
  • 6. College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan, China. [email protected].
  • # Contributed equally.
PMID: 41654705 DOI: 10.1038/s41538-026-00736-4
Abstract

T-2 toxin is a typical mycotoxin that seriously threatens human and animal health. Liver is the major target organ of T-2 toxin. To elucidate the precise hepatotoxicity mechanism and discover a natural antagonist of T-2 toxin. T-2 toxin (0, 0.5, 1, 2 mg/kg BW)-induced liver injury model, Ferrostatin-1 (1 mg/kg·BW) interference model, Parkin-/- mice model, Nrf2-activating model (tBHQ, 20 mg/kg·BW) and lycopene (5 mg/kg·BW) treatment model were constructed. Proteomics revealed that Ferroptosis is a critical hepatotoxicity mechanism of T-2 toxin. Blocking Ferroptosis alleviated the liver damage and Mitophagy under T-2 toxin threat. However, these processes were exacerbated in Parkin-/- mice. In vivo mouse model confirmed that Nrf2 activation increased PINK-Parkin mediated Mitophagy and alleviated T-2 toxin-induced Ferroptosis, suggesting that Nrf2/Mitophagy axis was involved in T-2 toxin-induced hepatic Ferroptosis. Further analysis revealed that lycopene promoted Nrf2 nuclear translocation and PINK-Parkin mediated Mitophagy to mitigate T-2 toxin-induced hepatic Ferroptosis.

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