Protection against deoxynivalenol (DON)-induced intestinal injury by sulforaphane via modulation of lysosomal function

  • J Hazard Mater. 2025 Dec 2:501:140687. doi: 10.1016/j.jhazmat.2025.140687.
Yeyi Xiao  1 ,  Xianrui Zheng  1 ,  Jie Wang  2 ,  Chao Xu  2 ,  Suwei Qiao  2 ,  Zongjun Yin  1 ,  Haifei Wang  3 ,  Wenbin Bao  4
Affiliations
  • 1. College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China.
  • 2. Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China.
  • 3. Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China. Electronic address: [email protected].
  • 4. Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China. Electronic address: [email protected].
PMID: 41352012 DOI: 10.1016/j.jhazmat.2025.140687
Abstract

Deoxynivalenol (DON) is a prevalent mycotoxin commonly detected in both human and animal diets, representing a significant health risk. Sulforaphane (SFN), a bioactive compound from Cruciferous vegetables known for its antioxidant. This study aimed to confirm SFN's protective effect against DON-induced intestinal injury and clarify its underlying molecular mechanism. In vivo, C57BL/6 male mice (n = 8/group) were treated with DON (2 mg/kg BW) and SFN (10 mg/kg BW) to assess the overall protective effects of SFN; in vitro, intestinal porcine epithelial cells (IPEC-J2) and pig intestinal organoids were treated with DON (1 μg/mL) and SFN (2 μM) to investigate the protective mechanism of SFN. Hematoxylin-eosin staining, western blot and flow cytometry were used to confirm the protective effects of SFN. RNA-seq, CETSA, ITDRF and non-targeted metabolomics was employed to investigate the mechanism of SFN supplementation. This study demonstrated that SFN significantly alleviated DON-induced intestinal toxicity: in vivo, SFN restored jejunal villus height/crypt depth and restored the balance of redox homeostasis (decreased MDA, LDH, SOD and CAT); in vitro, SFN lowered DON-induced cell Apoptosis and ROS accumulation. Mechanistically, lysosomal function was critical for SFN's protection-SFN directly targeted ATP6AP1 to enhance lysosomal acidification Moreover, ATP supplementation further potentiated this acidification and SFN's cytoprotective effect. This study identified ATP6AP1-mediated lysosomal acidification as a novel mechanism for SFN to mitigate DON-induced intestinal injury. Therefore, investigating the crosstalk between the SFN-ATP6AP1 axis and gut microbiota warrants further investigation to elucidate a broader protective mechanism.

Keywords
Deoxynivalenol; Intestine; Lysosome; Oxidative stress; Sulforaphane.
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