Oxidative stress affects intestinal health by inhibiting the differentiation of porcine intestinal epithelial cells through producing arachidonic acid

The intestinal epithelium is particularly vulnerable to oxidative stress caused by intracavitary stimulation, but the molecular mechanisms driving this damage remain poorly understood. The arachidonic acid (AA) pathway was significantly enriched in the transcriptome of in vivo oxidative stress-induced jejunum and in vitro oxidative stress-induced intestinal organoids, highlighting its critical role in mediating oxidative stress-induced epithelial injury. Additionally, oxidative stress elevated levels of AA in the jejunum in vivo, while the expression of genes related to epithelial differentiation, nutrient digestion, absorption, and transport was downregulated both in vivo and in AA-treated organoids in vitro. These findings indicated that oxidative stress disrupts intestinal epithelial cell differentiation through AA, leading to impaired intestinal function. Notably, inhibiting AA release not only enhanced organoid viability under oxidative stress but also reduced inflammatory responses in mice exposed to oxidative stress, demonstrating that AA serves as a key effector molecule in mediating oxidative stress-induced intestinal injury. By employing organoid models, this study clarified the pathological involvement of AA in oxidative stress-related intestinal injury, offering novel perspectives for potential therapeutic interventions in oxidative stress-associated gastrointestinal disorders.