P-198 - Relationship between aspirin-induced small intestinal mucosal injury and oxidative stress

Abstract

Background Endoscopic observation has clearly demonstrated the intestinal mucosal damage induced by aspirin, however, its mechanism remains unclear. We have reported that aspirin induces oxidative stress in the small intestinal epithelial cells. Aim The aim of this study is to investigate the involvement of oxidative stress on aspirin-induced small intestinal mucosal damage by using nuclear factor-erythroid 2-related factor 2 knock out (nrf2KO) mice, in which anti-oxidative defense system is disturbed. Method Under the anesthesia, aspirin (2–10 mg/body) suspended in 0.5% methylcellulose was injected into the proximal duodenum of C57Bl/6 wild type (WT) and nrf2KO mice (male, 8 weeks old). At 1.5 h after treatment, the mice were killed with ether and the small intestine was removed for histological examination. Result Aspirin significantly caused small intestinal mucosal injury in WT mice as assessed histologically in a concentration-dependent manner. Although low concentration of aspirin did not cause small intestinal mucosal injury in WT mice, it caused significant mucosal damage in nrf2KO mice. Conclusion The deficient of nrf2-driven oxidative stress detoxification pathway is important for the protection against aspirin-induced small intestinal mucosal injury.