Oxidative Stress Pathway Driven by Inflammation in Gastric Mucosa

Abstract

Oxidative stress is a state in which toxic reactive oxygen species (ROS) overcomes the endogenous antioxidant defence of the host (Bulger & Helton, 1998). This state results in an excess of free radicals, which can react with cellular lipids, proteins, and nucleic acids, leading to cellular injury and eventual organ dysfunction. Gastric inflammation is a highly complex biochemical protective response to cellular/tissue injury. A large amount of evidence suggests that Helicobacter pylori (H. pylori) infection and nonsteroidal antiinflammatory drug (NSAID) ingestion are major causative factors in the pathogenesis of gastric mucosal oxidative injury in humans. In response to H. pylori infection or NSAID, neutrophils are recruited to the site of inflammation and generate ROS and nitrogen reactive species (RNS) (Yoshikawa & Naito, 2000; Naito & Yoshikawa, 2002). The sources of radicals are mucosal xanthine oxidase and NADPH oxidase found in the resident leukocytes of the lamina propria (Otamiri & Sjodahl, 1991). However, recent results suggest that NOX family of NADPH oxidases might also be expressed in gastric epithelial cells. ROS mediates inflammation by activating redox-sensitive transcription factors such as NF-kappaB and activator protein (AP)-1 which upregulate a number of proinflammatory genes, resulting in the production of proinflammatory cytokines, adhesion molecules, receptors, etc. The generation of ROS and cytokines not only that is associated but also amplifies each other (positive feedback regulation). Not only is increased ROS formation a trigger of inflammation but inflammation itself again triggers ROS production (Glorie et al., 2006).