l-Carnosine Protects Against Deoxynivalenol-Induced Oxidative Stress in Intestinal Stem Cells by Regulating the Keap1/Nrf2 Signaling Pathway.

ABSTRACT

SCOPE The intestinal epithelium is nourished by various nutrients and subjected to persistent and widespread feed-derived mycotoxin stress. l-Carnosine (LC) possesses robust antioxidant activity; however, its role in protecting intestinal mucosa against deoxynivalenol (DON) is still unclear. METHODS AND RESULTS: In this study, 300 mg kg-1 BW LC and 3 mg kg-1 BW DON are orally administered to mice either alone or in combination for 10 days to investigate the role of LC in protecting the intestine against DON. This study found that LC alleviates the growth retardation of mice and repairs the damaged jejunal structure and barrier functions under DON exposure. LC rescues the intestinal stem cells (ISCs), increases the growth advantage in enteroids derived from jejunal crypts of mice in each group ex vivo, improves the proliferation and apoptosis of intestinal cells, and promotes ISC differentiation into absorptive cells, goblet cells, and Paneth cells. Furthermore, LC activates Nrf2 signaling by binding to Keap1 to reverse the striking DON-induced increase in ROS levels. CONCLUSION: The study findings unveil that LC potentiates the antioxidant capacity of ISCs by regulating the Keap1/Nrf2 signaling pathway, which contributes to the intestinal epithelial regeneration response to DON insult.