Selenium (Se) has a significant role in stimulating the immune system. Intake of Se can increase oxidative defense and alleviate oxidative stress1,2. It is known that Se has anti-inflammatory and antioxidant effects3,4. Se supplementation inhibited the activation of the nuclear transcription factor kappa - light chain enhancer (NF- κB) by increasing the expression of protein, and enhanced the mucosal immune function of the duodenum of chicks5. Necessary intake of Se is beneficial for inflammatory diseases, which have regulatory protein functions in many signal transduction pathways6. Se levels and Se protein gene expression in the body depend on adequate Se diet supply7. Se in food products most often occurs in combination with proteins, thus products with high protein content are typically characterized by a higher Se content8. People should pay attention to the use of Se elements, such as finished protein-mineral preparations, in the manufacture of high-quality consumer foods to enrich those diets that are deficient in Se9. Seleniummethionine (SeMet) is an organic selenium compound, and SeMet is often used to treat Se deficiency due to its low toxicity and easy absorption. SeMet has been found to have a variety of biological activities, including strengthening the immune system and improving antioxidant performance10. SeMet can reduce oxidative stress. Prolonged administration of SeMet increases the concentration of selenium in the blood. Whether SeMet supplementation increased GPX1, GPX2 and GPX4 (GPXs) activity in chick tissues and organs11. SeMet can affect the REDOX regulation function, and downregulation of Rap1/MAPK/ERK signaling pathway has a protective effect on oxidative stress12. SeMet provides Se for the synthesis of selenoproteins such as Gpx1. Se-Met can enhance antioxidant capacity and reduce oxidative stress13,14.
Intestinal dysfunction and intestinal obstruction is caused by ischemia-reperfusion (I/R) injury, which is a common problem in dysfunction surgery. I/R can lead to tissue damage associated with inflammation and intestinal mucosal apoptosis15. When I/R occurs in the intestinal tissues, it begins with a series of cellular events. During I/R, reperfusion can cause intestinal injury in addition to ischemia16,17. During ischemia, intracellular energy storage decreases18. Cell dysfunction induced by I/R is considered to be an important factor in cell damage. Cell damage caused by I/R leads to cell structure change and dysfunction, such as cell metabolism disorder, cell necrosis and apoptosis19.
Apoptosis is a characteristic pathological change caused by I/R. Furthermore, I/R induced apoptosis may be one of the mechanisms of delayed intestinal injury. This phenomenon can now be explained by the production of hydroxyl radicals during ischemia, which alter the structure of fibrinogen by blocking blood flow in the blood vessels20. Small intestinal I/R injury causes local production of ROS, it plays an important role in intestinal epithelial injury21. I/R increased oxidative stress, leading to mitochondrial damage, which aggravated I/R damage22. Mitochondrial injury causes cytochrome c (Cyt-c) of mitochondrial protein to be released into cytoplasm, in which Cyt-c is involved in activation of caspase-3, leading to apoptosis23,24,25. Bcl2-related X protein (Bax) interacts with Bcl-2 and participates in the regulation of apoptosis26,27. Bcl-2 plays an antiapoptotic role, while Bax promotes apoptosis. The ratio of bcl-2 to Bax could be down-regulated to control cleaved caspase-328,29. Activation of caspase-3 induces apoptosis.
A previous study found that sodium selenite pretreatment reduced I/R induced cardiac injury in rats30. SeMet supplementation could modulate the extent of cellular damage observed in an in vitro cardiac myocyte model exposed to (patho)-physiological levels of hypochlorous acid and an in vivo rat model of cardiac I/R injury31. However, little is known about the correlation of SeMet on I/R-induced intestinal apoptosis by the mitochondrial pathway. These facts led to an experimental study of the role of SeMet pretreatment in the mice intestinal I/R model. In this study we established the intestinal I/R injury model in the mice, evaluated the improvement of SeMet on I/R induced intestinal damage, and studied its mechanism. Our I/R injury model was pretreated with SeMet to obtain intestinal tissues of mice and observe its biological changes. In this study, glutathione peroxidase-1(Gpx1), catalase (CAT) and superoxide dismutase (SOD) activities and malondialdehyde (MDA) content were measured in the mice intestinal tissues. Fluorescence quantitative PCR (qPCR) and Western blot were used to quantify the levels of apoptosis-related genes (Bcl-2, Bax, Cyt-c, and caspase-3) in the mice intestinal tissues. Therefore, the purpose of this study was to investigate the effect of SeMet on the mice intestinal lipid peroxidation and apoptosis, to identify the mechanism of Se alleviates I/R induced apoptosis.