Involvement of the Xanthine-Xanthine Oxidase System and Neutrophils in the Development of Acute Gastric Mucosal Lesions in Rats with Water Immersion Restraint Stress

Abstract

In rats subjected to water immersion restraint (WIR) stress for 1, 3, and 6 h, gastric mucosal lesions developed time-dependently with an increase in lipid peroxide (LPO) levels and a decrease in nonprotein sulfhydryl levels in the gastric mucosa. The gastric mucosal xanthine oxidase (XO) activity significantly increased with the conversion of xanthine dehydrogenase (XD) to XO at 6 h of WIR (3.2-fold that of the control group without WIR). A significant increase in myeloperoxidase (MPO) activity, an index of neutrophil infiltration, occurred in the gastric mucosa at 3 and 6 h of the WIR (2.2- and 3.3-fold that of the control group without WIR, respectively). In contrast, superoxide dismutase, catalase, and glutathione peroxidase activities in the gastric mucosa did not change during the WIR period. Pretreatment with either allopurinol (AP), an inhibitor of XO, or soybean trypsin inhibitor (STI), a serine protease inhibitor, attenuated the lesion development at 6 h of WIR, but not at 3 h. In the gastric mucosa of rats pretreated with AP, enhancements of LPO formation, sulfhydryl oxidation, and XO activity found at 6 h of WIR were prevented with inhibition of XD plus XO activity, while in the gastric mucosa of rats pretreated with STI, these enhancements were prevented with inhibition of the conversion of XD to XO. In the gastric mucosa of rats pretreated with anti-polymorphonuclear leukocyte antiserum, the lesion development and enhanced LPO formation and sulfhydryl oxidation found at 3 and 6 h of WIR were prevented with a decrease in increased MPO activity. These results indicate that in the gastric mucosa of rats with WIR stress, the progression of lesions is mainly related to enhanced LPO formation and sulfhydryl oxidation which depend on an increased generation of oxygen free radicals via the xanthine-XO system and neutrophils rather than the change in the oxygen free radical-scavenging activity of antioxidant enzymes. The present results also suggest that increased gastric mucosal LPO formation and sulfhydryl oxidation found at 3 h of WIR could be mainly due to neutrophil-derived oxygen free radicals, while enhanced gastric mucosal LPO formation and sulfhydryl oxidation found at 6 h of WIR could be due to both neutrophil- and XO-derived oxygen free radicals.

Actions of L-citrulline on gastric mucus secretion and gastric mucous cell counts in albino rats

“…It can be readily converted to L-arginine, in the kidney, vascular endothelium and other tissues, thus raising its plasma and tissue levels. (Solomonson et al,2003).From this study, it was found that L-arginine increases the mucus secretion to 11.30±2.64**mg/tissue from 7.4±1.58*in the control as shown in Table 1, which supports the report by Liu et al,2008 andNishida et al,1997). As an indirect precursor of L-arginine, Lcitrulline has a cardioprotective effect, Previous studies have observed reduction in brachial BP after oral L-arginine supplementation in adults with high BP and concurrent chronic diseases (Palloshi et al, 2004).…”

Activation of p38 MAPK by Reactive Oxygen Species Is Essential in a Rat Model of Stress-Induced Gastric Mucosal Injury

“…Cold immobilization stress is a commonly used and clinically relevant experimental model for stress-induced gastric mucosal lesions (5)(6)(7). This model requires at least 6 h to form profound hemorrhagic necrotic lesions in the gastric mucosa (12,15). The finding of the current study showed that when rats were exposed to cold immobilization stress for a total of 6 h, phosphorylation/activation as well as activity of p38 kinase in gastric mucosa was remarkably up-regulated at as early as 15 min after the start of stress and still persisted until the end of stress.…”

“…Under this hypoxic-ischemic condition, reactive oxygen species (ROS) 4 such as superoxide anions, hydrogen peroxide, and hydroxyl radicals are rapidly and continuously produced, and the resulting oxidative stress is proven crucially responsible for the development and progression of epithelial necrosis and mucosal ulceration (10 -12). In addition, this hypoxic-ischemic condition is also accompanied by an acute inflammatory response of the gastric mucosa characterized by accumulation of inflammatory cells and a multitude of inflammatory mediators (13)(14)(15)(16). Recruitment and activation of neutrophils contribute greatly to the pathophysiological processes occurring in gastric mucosa at the later stage of stress (13,14).…”

“…Recruitment and activation of neutrophils contribute greatly to the pathophysiological processes occurring in gastric mucosa at the later stage of stress (13,14). Synthesis and release of inflammatory mediators, especially of proinflammatory cytokines such as TNF-␣, IL-1␤, and IL-18, of chemokines such as cytokine-induced neutrophil chemoattractant-1 (CINC-1, a rat analog of human IL-8/Gro-␣ and a potent neutrophil chemoattractant), and of adhesion molecules such as ICAM-1 as well as of inducible NO synthase/NO, are recently emerged as important determinants of mucosal inflammation and gastric injury following cold immobilization stress (15)(16)(17)(18)(19)(20). However, despite intense research, much is unknown about the molecular mechanism or the signal transduction mechanism by which this type of stress induces the incidence of acute gastric mucosal injury.…”

Effect of Dietary Vitamin E Supplementation on Liver Oxidative Damage in Rats with Water-Immersion Restraint Stress

“…Reactive oxygen species (ROS) and nitric oxide ( • NO) generation, lipid peroxidation, and neutrophil infiltration in the gastric mucosal tissue play a critical role in the pathogenesis of WIRS-induced gastric mucosal lesions (2)(3)(4)(5).…”