117 - Role of Oxidative Stress in Acetyl Salicylic Acid (ASA)-Induced Small Intestinal Injury in Rats

Abstract

Background and Aim Although ASA-induced small intestinal mucosal injury has been reported to be quite common, the pathogenesis is not yet. We have reported ASA increases small intestinal epithelial cell permeability as a first step of small intestinal mucosal injury via ROS and ROS-modified ZO-1 protein using an in vitro model. In this study, we clarified the pathogenesis using an ex vivo and an in vivo model. Methods In an in vivo study, ASA (200mg/kg) was injected into the proximal duodenum of rats (male Sprague-Dawley, 9 weeks old). After treatment, the small intestine was removed for histological examination and 1% Evans blue was injected (i.v.) to visualize intestinal lesions. In an ex vivo study, we measured ASA (50-200mM)-induced small intestinal mucosal permeability using the Ussing chamber by assessing the flux of FITC-dextran. ASA-induced oxidative stress in small intestine was assessed by the expression of HNE-modified protein using western blotting. Results In an in vivo study, ASA induced mucosal injury, especially in the jejunum, that was confirmed by the histological and Evans blue methods. In an ex vivo study, ASA increased the flux of FITC-dextran in a concentration dependent manner. At the same time, ASA increased HNE-modified proteins in small intestine. Conclusion ASA-induce small intestinal injury can be caused by increased oxdative stress in the mucosa.