Ferroptosis is involved in deoxynivalenol-induced intestinal damage in pigs

Abstract 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 = 7/group) were fed a control diet, or diet adding 1.0 or 3.0 mg DON/kg. At week 4, serum and small intestines were 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.