Inhibition of p38 MAPK activation attenuates esophageal mucosal damage in a chronic model of reflux esophagitis

Abstract Background Reflux esophagitis ( RE ) is one of the common gastrointestinal diseases that are increasingly recognized as a significant health problem. This study was designed to investigate the role of p38 mitogen‐activated protein kinase ( MAPK ) in experimental chronic RE model of rats. Methods Chronic acid RE rats were induced by fundus ligation and partial obstruction of the pylorus and treated with SB 203580 (a p38 MAPK inhibitor, i.p., 1 mg/kg/day) for 14 days. Key Results Immunohistochemical staining and Western blotting results revealed the activation of p38 MAPK signaling in the esophagus mucosa 14 days post injury. Through gross and histological assessment, we found that inhibition of p38 MAPK activation by SB 203580 attenuated esophageal mucosal damage in RE rats. Inhibition of p38 MAPK activation in RE rats attenuated esophageal barrier dysfunction, through enhancing the expression of tight junction proteins and reducing the expression of matrix matalloproteinases‐3 and ‐9. Inhibition of p38 MAPK activation in RE rats reduced CD 68‐positive cells in esophagus mucosa and mRNA levels of tumor necrosis factor (TNF)‐ α , interleukin (IL)‐6, and IL ‐1 β in esophagus and protein levels of TNF ‐ α , IL ‐6, and IL ‐1 β in serum. In addition, we found that inhibition of p38 MAPK activation in RE rats suppressed protein expression of inducible nitric oxide synthase and reduced formation of nitric oxide ( NO ), 3‐nitrotyrosin, and malondialdehyde in esophagus. Conclusions & Inferences Inhibition of p38 MAPK activation attenuated esophageal mucosal damage in acid RE rats, possibly by modulating esophageal barrier function and regulating inflammatory cell recruitment, and the subsequent formation of cytokines, NO , and reactive oxygen species.