Curcumin Alleviates DON-Induced Intestinal Epithelial Barrier Disruption by Improving Ribotoxic Stress-Associated p38...

Area of Science:

• Gastroenterology
• Toxicology
• Molecular Biology

Background:

• Deoxynivalenol (DON) is a mycotoxin causing intestinal barrier dysfunction.
• Curcumin (CUR) exhibits enteroprotective effects, but its mechanisms against DON are unclear.

Purpose of the Study:

• Investigate CUR's protective mechanisms against DON-induced intestinal epithelial injury.
• Elucidate CUR's role in regulating tight junctions, apoptosis, cell cycle, and the ribosomal stress response (RSR) pathway.

Main Methods:

• In vivo (mice) and in vitro (IPEC-J2 cells) models of DON-induced intestinal injury.
• Assessed intestinal permeability, tight junction protein expression (Claudin-4, occludin), F-actin.
• Evaluated apoptosis (p53, caspase), cell cycle arrest (p21), and RSR-associated p38 pathway activation (p38, GSK3β, ATF-2 phosphorylation).

Main Results:

• CUR reduced DON-induced intestinal permeability by restoring Claudin-4 and occludin, and preventing F-actin contraction.
• CUR attenuated DON-induced apoptosis and G1 cell cycle arrest.
• CUR inhibited the RSR-associated p38 pathway; p38 activation reversed CUR's protective effects.

Conclusions:

• CUR alleviates DON-induced intestinal epithelial barrier disruption.
• CUR acts by modulating the RSR-associated p38 pathway, thereby protecting tight junctions, reducing apoptosis, and normalizing cell cycle arrest.
• CUR shows potential as a therapeutic agent for mycotoxin-induced intestinal dysfunction.