Study On The Toxic Effects Of Vomitoxin On The Liver And Kidney Of Weaned Rabbits Through MAPKs Signaling Pathway And Metabolomicss

Deoxynivalenol(DON),also known as vomitoxin(VT),is widely distributed in grain-based feeds and foods.The widespread distribution and multiple toxic effects of DON have caused serious harm to human health and the development of livestock and poultry industry.In recent years,China’s rabbit industry has developed rapidly,the complete feed has been widely used in rabbit breeding,which significantly increased the risk of mycotoxin contamination in rabbit feed.The studies on the toxicity of DON at China and abroad are mostly focused on pigs and poultry.There are few studies about the DON on rabbits.In this study,the toxic effects of DON on the liver and kidney of weaned rabbits were analyzed based on MAPKs signaling pathway and metabolomics.Forty-five weaned rabbits were random Ly divided into three groups(no difference in initial body weight,879.79±17.62g),which were Control group(Control group),LD group(DON low-dose group,DON 0.5mg/kg·BW)and HD group(DON high-dose group,DON1.5mg/kg·BW).The prefeeding period was 7 days.After the experiment began,the test animals were given DON every other day for 12 times.At the test day 8,16 and 24 days pouring DON before(0 h)and pouring DON after 1 h,2 h,3 h,4 h,6 h,Control group and the HD group selected eight rabbit ear margin vein blood sampling,and collected on an empty stomach 24 rabbits and urine samples,in experimental 25 th day take irrigation DON rabbit serum and urine samples to carry out LC/MS analysis.After the feeding experiment,samples of liver,kidney and ileum,cecum,colon contents were collected.The liver and kidney tissues were fixed with paraformaldehyde for histological observation,immunohistochemical assay,Western-blot and RT-PCR assay.The intestinal contents were sequenced and analyzed by 16 S r DNA.Results: The liver and kidney tissue structures of weaned rabbits were obviously damaged after DON administration.The m RNA and protein expressions of p38,ERK and JNK in liver and kidney tissues of young rabbits were significantly increased,and the distribution of p38,ERK and JNK positive reactants was also significantly expanded,and their expression levels were affected by the supplemental dose of DON.Metabonomics data show that potential biomarkers in the serum is primarily concerned with glycerol phospholipid metabolism,tryptophan metabolism and pentose and mutual transformation between glucose acid ester,and urine biomarkers caffeine metabolism,glycine,serine and threonine metabolism and biosynthesis of terpenoids backbone.Correlation analysis suggested that DON could induce changes of some disease-related metabolites in serum and urine.16 S r DNA showed that the relative abundance and diversity of microflora in ileum,cecum and colon of weaned rabbits were decreased by DON intake,especially in ileum and cecum.In conclusion,DON can lead to metabolic abnormalities and intestinal flora disorder in weaned rabbits,and damage liver and kidney health by affecting protein expression of MAPKs signaling pathway.