Effect of zearalenone on the jejunum of weaned gilts through the Epac1/Rap1/JNK pathway.

ABSTRACT

Zearalenone (ZEN) is a nonsteroidal estrogenic mycotoxin produced by Fusarium strains that is harmful to the intestinal health of animals and is widely present in contaminated crops. The objective of this study was to investigate the potential therapeutic target of ZEN-induced jejunal damage in weaned gilts. Sixteen weaned gilts either received a basal diet or a basal diet supplemented with 3.0 mg/kg ZEN in a 32-d experiment. The results showed that ZEN at the concentration of 3.0 mg/kg diet activated the inflammatory response and caused oxidative stress of gilts (P < 0.05). ZEN exposure resulted in the upregulation (P < 0.05) of the Exchange protein directly activated by the cAMP 1/Ras-related protein1/c-Jun N-terminal kinase (Epac1/Rap1/JNK) signaling pathway in the jejunum of gilts in vivo and in the intestinal porcine epithelial cells in vitro. The cell viability, EdU-positive cells, and the mRNA expression of B-cell lymphoma-2 (Bcl-2) were decreased, whereas the reactive oxygen species production and the mRNA expressions of Bcl-2-associated X (Bax) and Cysteine-aspartic acid protease 3 (Caspase3) were increased (P < 0.05) by ZEN. However, ZEN increased the mRNA expression of Bcl-2 and decreased the mRNA expressions of Bax and caspase3 (P < 0.05) after the Epac1 was blocked. These results collectively indicated that a 3.0 mg ZEN /kg diet induced jejunal damage via the Epac1/Rap1/JNK signaling pathway.

Mycotoxins have caused huge economic losses to livestock industry. This study assessed the impact of zearalenone (ZEN) on the jejunum of weaned gilts. Results revealed that significant inflammatory response and oxidative stress were stimulated by 3.0 mg/kg ZEN in the jejunum tissue of weaned gilts. Furthermore, the reactive oxygen species accumulation and apoptosis in the intestinal porcine epithelial cells (IPEC-J2) were triggered, respectively. The negative impact of ZEN on the jejunum was by activation of Epac1/Rap1/JNK signaling pathway in the jejunum and this could be reduced by blocking Epac1. A more comprehensive understanding of the underlying molecular mechanisms will facilitate the development of novel strategies to mitigate the detrimental effect of ZEN on the jejunum of weaned gilts.