Ferroptosis is involved in deoxynivalenol-induced intestinal damage in pigs

Background Deoxynivalenol(DON)is a widespread issue for feed and food safety,leading to animal and human health risks.The objective of this study was to determine whether ferroptosis is involved in DON-induced intestinal injury in piglets.Three groups of 21-day-old male weanling piglets(n 4,serum and small intestines were=7/group)were fed a control diet,or diet adding 1.0 or 3.0 mg DON/kg.At week collected to assay for biochemistry,histology,redox status and ferroptosis-related genes expression.In addition,the involvement of ferroptosis and the role of FTL gene in DON-induced cell death were further verified in the IPEC-J2 cells.Results Compared to the control,dietary supplementation of DON at 1.0 and 3.0 mg/kg induced different degrees of damage in the duodenum,jejunum and ileum,and increased(P<0.05)serum lipopolysaccharide concentration by 46.2%-51.4%.Dietary DON supplementation at 1.0 and(or)3.0 mg/kg increased(P<0.05)concentrations of malondialdehyde(17.4%-86.5%)and protein carbonyl by 33.1%-92.3%in the duodenum,jejunum and ileum.In addition,dietary supplemented with DON upregulated(P<0.05)ferroptotic gene(DMT1)and anti-ferroptotic genes(FTL and FTH1),while downregulated(P<0.05)anti-ferroptotic genes(FPN,FSP1 and CISD1)in the duodenum of the porcine.Furthermore,the in vitro study has demonstrated that deferiprone,a potent ferroptotic inhibitor,mitigated(P<0.05)DON-induced cytotoxicity in porcine small intestinal IPEC-J2 cells.Additionally,deferiprone prevented or alleviated(P<0.05)the dysregulation of ferroptosis-related genes(ACSL4 and FTL)by DON in IPEC-J2 cells.Moreover,specific siRNA knockdown FTL gene expression compromised the DON-induced cell death in IPEC-J2 cells.Conclusions In conclusion,this study revealed that ferroptosis is involved in DON-induced intestinal damage in porcine,and sheds a new light on the toxicity of DON to piglets.