Protective Effect Of Selenomethionine On Ochratoxin A-induced Intestinal Barrier Damage In Rabbits

Mycotoxins are highly diverse secondary metabolites produced by a variety of fungi in nature,which can contaminate food as grain feed and cause serious harm to human and animal health.Among mycotoxins family,Ochratoxin A（OTA）is second only to aflatoxin in importance and harmfulness,and it is widely distributed.In addition,OTA is also classified as one of the three major groups of enteropathogenic mycotoxins.When OTA-contaminated food is ingested by animal,OTA will be continuously accumulated and increased in the body,and it is difficult to be excreted with metabolism,which seriously threatens the health of humans and animals.At this stage,OTA are often detected in cereals and animal products.Therefore,how to reduce the toxic effects of OTA on animal organisms has become a major issue we face.Selenium is considered to be one of the trace elements necessary for animal body to maintain normal physiological functions.In recent years,a large number of studies have pointed out that selenium has a significant effect on the prevention of mycotoxin poisoning.In this study,selenomethionine（Se Met）was used as a supplementary selenium source to explore the preventive effect of selenium on OTA-induced intestinal barrier damage in rabbits.Methods:In this experiment,60 35-day-old meat rabbits with similar body weight were randomly divided into 5 groups w ith 12 rabbits in each group.These groups were control group,OTA group（0.2 mg/kg OTA）,OTA+0.2 mg/kg Se group（0.2 mg/kg OTA+0.2 mg/kg Se）,OTA+0.4 mg/kg Se group（0.2 mg/kg OTA+0.4 mg/kg Se）,OTA+0.6 mg/kg Se group（0.2 mg/kg O TA+0.6 mg/kg Se）.Then,the rabbits in OTA+0.2 mg/kg Se group,OTA+0.4 mg/kg Se group and OTA+0.6 mg/kg Se group were fed diets containing different doses of selenomethionine,respectively.And the rabbits in the control group and OTA group were fed the basal diet for 21 d.OTA was dissolved in Na HCO₃ solution.After that,on the 15th day,rabbits in OTA group,OTA+0.2 mg/kg Se group,OTA+0.4 mg/kg Se group and OTA+0.6 mg/kg Se group were orally fed with OTA at a dose of 0.2 mg/kg,and rabbits in control group were perfused with the same volume of Na HCO₃ solution for 7 d.During the experiment,the rabbits were provided with sufficient food and water.During the experiment,the body weight and daily feed intake of the rabbits were recorded.After the experiment,the serum and jejunum tissue of the rabbits were collected.The length of villis and the depth of crypts in the small intestine were detected by HE staining,the number of jejunal goblet cells were detected by PAS staining,the proliferation of jejunal PCNA was detected by immunohistochemistry,the changes of antioxidant levels in jejunum tissue were detected by kits,and the expression levels of NF-κB and Nrf2 signaling pathway-related genes m RNA and marker proteins were detected by q PCR and ELISA.Results:The results showed that:（1）Se Met pretreatment had a protective effect on the changes in serum biochemical indexes and the decline in production performance caused by O TA exposure,among which 0.4 mg/kg dose of Se Met pretreatment has the best effect.（2）Se Met pretreatment could inhibit OTA exposure-induced oxidative damage in rabbit jejunum tissue by stimulating the expression of Nrf2 and HO-1,increasing SOD activity,GSH-PX activity,T-AOC and ROS content,and reducing MDA content,among which 0.4 mg/kg dose of Se Met pretreatment has the best effect.（3）Se Met pretreatment can inhibit OTA exposure-induced intestinal barrier damage in rabbits by increasing the length of jejunal villi,the number of goblet cells,and the expression levels of jejunal PCNA protein and tight junction proteins（C laudin-1,Occludin,and ZO-1）,among which 0.4 mg/kg dose of Se Met pretreatment has the best effect.（4）Se Met pretreatment can inhibit OTA exposure-induced inflammatory injury in rabbit intestinal tissue by inhibiting the NF-κB signaling pathway and down-regulating the expressions of inflammatory factors TNF-α,IL-1β,and IL-6,among which 0.4 mg/kg dose of Se Met pretreatment has the best effect.Conclusions:The above results show that Se Met can improve the OTA-induced intestinal barrier damage and production performance decline in rabbits through the regulation of Nrf2 and NF-κB signaling pathways,and the 0.4 mg/kg Se Met group has the most significant effect.