Ferroptosis is Involved in Deoxynivalenol-induced Intestinal Damage in Pigs

Overview

Journal J Anim Sci Biotechnol

Publisher Biomed Central

Date 2023 Mar 16

PMID 36922863

Authors

Meng Liu

Lei Zhang

Yixin Mo

Jiahuan Li

Jiacheng Yang

Juan Wang

Niel Alexander Karrow

Hao Wu

Lvhui Sun

Affiliations

Soon will be listed here.

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.

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