Selenium deficiency induces duodenal villi cell apoptosis via an oxidative stress-induced mitochondrial apoptosis pathway and an inflammatory signaling-induced death receptor pathway.

Selenium (Se) is an important nutritional trace element possessing antioxidant properties. Our goal was to elucidate the effect and mechanism of Se deficiency on the intestinal cell fate. One-day-old three-yellow chickens were fed a low Se diet for 1, 3, and 5 weeks. Histologic characteristics, protein expression profiles, antioxidant activities, inflammatory signaling, and the apoptosis status in duodenum mucosa were investigated. Histological results showed that Se deficiency could increase inflammatory cell infiltration, karyopyknosis of the epithelial cells, cytoplasm vacuolization and dissolution of goblet cells. The proteomics results indicated that Se deficiency could induce apoptosis of cells in duodenal villi via inhibition of antioxidant redox signaling and activation of NF-κB signaling. Further analysis results showed that Se deficiency decreased the total antioxidant capacity of duodenum mucosa via down-regulating the transcription level and activities of glutathione peroxidase (GPX), reduced glutathione (GSH), and thioredoxin reductase (TrxR). The NF-κB signaling pathway was activated by Se deficiency-induced reactive oxygen species (ROS). TUNEL, DNA ladder, immunohistochemical assay, and western blotting proved that selenium deficiency could induce duodenal villi cell apoptosis. The results also indicated that Se deficiency can cause duodenal villi cell apoptosis via an oxidative stress-induced mitochondrial apoptosis pathway (intrinsic pathway) and an inflammatory signaling-induced death receptor pathway (extrinsic pathway). Our data may provide new insight into the prevention and treatment of chronic diarrhea caused by Se deficiency.