Role of bile acids, prostag landins and COX inhibitors in chronic esophagitis in a mouse model

AIM. To develop a new experimental model of esophagitis that serves a complementary tool to clinical investigation in an insight into the mechanism of the damage to the esophagus mucosa by aggressive factors, and role of COX inhibitors in this process. METHODS： The study was conducted in 56 male mice. Animals were divided into seven groups： （1） perfused with HCI, （2） perfused with HCI and physiologic concentration of pepsin （HCI/P）, （3） perfused with similar HCI/P solution enriched with conjugated bile acids （glycho- and tauro-sodium salts） designated esophageal infusion catheter under the general anesthesia, （4） perfused as in group 2 treated with indometacin, （5） perfused as in group 2 treated with NS-398, （6） perfused as in group 3 treated with indometacin, and （7） perfused as in group 3 treated with NS-398. The esophagus was divided into 3 parts： upper, middle and lower. The PGE2 concentration was measured in all parts of esophagus using RIA method. Esophagus of sacrificed animals was macroscopically evaluated using a low power dissecting microscope （20x）. Specimeris, representing the most frequently seen changes were fixed, stained with H＆E and assessed microscopically using the damage score, and inflammatory score. RESULTS： The macroscopic changes were significantly severer in HCI/P than those in HCI animals （77%） and in HCI/P/BA group （43%）. In HCI/P NS-398 group we noticed significantly less changes than those in not treated group （42%） and in analogical group treated with indometacine （45%）. In HCI/P/BA INDO group we observed significantly severer changes than that in not treated group （52%）. We noticed less changes in HCI/P NS-398 than that in group with indometacine （46%）. In HCI/P/BA NS-398 group we had less changes than that in indometacin group （34%）. The microscopic changes observed in HCI/P/BA INDO group were severer than that in not treated group （48%）. Esophagitis index in HCI group was significantly lower than in HCI/P and also HCI/P/BA group （32% and 33 %）. In HCI/P/BA/INDO group the esophagitis surface was larger than that in not treated group （33%）. In HCL/P group the surface of esophagus with ulceration was significantly larger （10-fold） than that in HCI/P/BA group. The PGE2 concentration was significantly higher in HCI/P group than in HCI/P/BA group. The PGE2 concentration in lower part of esophagus was also significantly higher in middle than those in HCI and HCI/P/BA groups. In upper part of esophagus the PGE2 concentration was significantly higher in HCI/P/BA group than that in group treated with indometacine （46%）. We also observed higher PGE2 concentration in middle part of esophagus in HCI/P/BA group than those in group treated with indometadne and in group treated with indometacin and NS-398 （by 52% and 43% respectively）. CONCLUSION： Pepsin is the pivotal factor in the development of chronic esophageal injury. Bile acids diminish chronic esophageal injury induced by HCI/P, indicating its potential negative impact on pepsin proteolytic potential, pivotal for mucosal injury in low pH. The role of selective COX inhibitors is still unclear, and needs more investigations. This novel chronic experimental esophagitis is an excellent model for further study on the role of cytokines in genetically modified animals.