Sodium Butyrate Ameliorates Deoxynivalenol-Induced Oxidative Stress and Inflammation in the Porcine Liver via NR4A2-Mediated Histone Acetylation

Mycotoxin-induced liver injury is often accompanied byoxidativestress (OS) and inflammation. This research aimed to explore the potentialmechanism of sodium butyrate (NaBu) in modulating hepatic anti-oxidationand anti-inflammation pathways in deoxynivalenol (DON)-exposed piglets.The results show that DON induced liver injury, increased mononuclearcell infiltration, and decreased serum total protein and albumin concentrations.Transcriptomic analysis revealed that reactive oxygen species (ROS)and TNF-& alpha; pathways were highly activated upon DON exposure.This is associated with disturbed antioxidant enzymes and increasedinflammatory cytokines secretion. Importantly, NaBu effectively reversedthe alterations caused by DON. Mechanistically, the ChIP-seq resultrevealed that NaBu strongly depressed DON-increased enrichment ofhistone mark H3K27ac at the genes involved in ROS and TNF-& alpha;-mediatedpathways. Notably, we demonstrated that nuclear receptor NR4A2 wasactivated by DON and remarkably recovered with the treatment of NaBu.In addition, the enhanced NR4A2 transcriptional binding enrichmentsat the promoter regions of OS and inflammatory genes were hinderedby NaBu in DON-exposed livers. Consistently, elevated H3K9ac and H3K27acoccupancies were also observed at the NR4A2 binding regions. Takentogether, our results indicated that a natural antimycotic additive,NaBu, could mitigate hepatic OS and inflammatory responses, possiblyvia NR4A2-mediated histone acetylation.

Automated summary

This research investigates the potential mechanism of sodium butyrate (NaBu) in modulating hepatic anti-oxidation and anti-inflammation pathways in deoxynivalenol (DON)-exposed piglets. The findings suggest that NaBu effectively reverses the liver injury, mononuclear cell infiltration, and decreased serum protein concentrations caused by DON, possibly through NR4A2-mediated histone acetylation. This highlights the potential of NaBu as a natural antimycotic additive in mitigating hepatic oxidative stress and inflammatory responses.