The role of intestinal CYP2E1 in pathophysiology of the gastrointestinal tract disorders: new therapies for leaky gut syndrome and inflammatory bowel diseases

<p>Leaky gut syndrome (LGS) is observed in numerous gastrointestinal (GI) disorders, including inflammatory bowel diseases (IBD)</p><p>characterized by chronic inflammation affecting the GI tract. It is well-established that the activity of CYP2E1 may</p><p>contribute to the severity of inflammation due to the production of ROS.</p><p>The main aim of the project is to evaluate the effect of CYP2E1 inhibitors as potential drugs maintaining intestinal permeability and alleviating intestinal inflammation</p><p>in vitro and in vivo. Although intestinal CYP2E1 is expressed in rodents and humans, still little is known about its expression</p><p>in inflamed intestinal tissues. Here, we examined the changes of CYP2E1 level in the gut during</p><p>inflammation in mice and IBD patients.</p><p>In in vitro phase, we evaluated the effect of CYP2E1 selective inhibitors on epithelial barrier integrity and</p><p>inflammation. We verified the hypotheses that treatment with analogs of diallyl sulfide (DAS) protects against increased</p><p>permeability and ameliorates inflammatory response of Caco-2 cells. In the second phase, we evaluated the influence</p><p>of selected CYP2E1 inhibitor on epithelial barrier integrity and inflammation in vivo. We used mouse models</p><p>of: (i) high fructose-induced LGS and inflammation and (ii) dextran sulfate sodium-induced colitis. In the translational part of the project, we used ELISA to examine the expression of CYP2E1 protein</p><p>in inflamed colon samples from humans. Moreover, we will investigated into potential associations between</p><p>CYP2E1 level, the expression of proteins involved in intestinal barrier integrity, and selected disease parameters of IBD.</p>