dimethylarginine and Stomach-Ulcer

Nitric oxide (NO) is a well-known gastric mucosa protection factor. Recently, it has been reported that methylated arginine compound such as asymmetric dimethylarginine (ADMA), which inhibits nitric oxide synthesis, may be related to the development of gastric mucosa injury in patients with Helicobacter pylori infection. In the present study, we tested the relationship between endogenous ADMA and gastric mucosa injury in H. pylor- infected patients and cultured gastric epithelial cells.. One hundred and fifty subjects with gastric diseases were entered in this study. The levels of ADMA in gastric juice and plasma were measured in both H. pylori+ and H. pylori- patients. We analyzed independent risk factors that contribute to ADMA levels by multiple linear regression analyses. Mucosal epithelium cells were treated with nicotine (10 microM) for 24 hours in the presence or absence of H. pylori. The concentrations of ADMA in the culture medium and the rate of cell apoptosis were determined.. The ADMA level in gastric juice was significantly increased in H. pylori+ patients (P<0.05), whereas there were no differences in the content of ADMA in the plasma between H. pylori+ patients and H. pylori- patients. Smoking and H. pylori infection were 2 independent risk factors contributing to ADMA levels, and in the population of H. pylori+ patients, the level of ADMA in smokers was higher compared with nonsmokers. Incubation of nicotine (10 microM) with epithelial cells for 24 hours further increased the elevated level of ADMA and the rate of cell apoptosis owing to H. pylori infection.. H. pylori infection caused an increase of ADMA levels in gastric juice, which was aggravated by smoking. Endogenous ADMA may be an important factor contributing to gastric mucosa injury.

Topics: Adolescent; Adult; Apoptosis; Arginine; Cells, Cultured; Female; Gastric Juice; Gastric Mucosa; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Linear Models; Male; Middle Aged; Nicotine; Nitric Oxide; Stomach Ulcer; Young Adult

Our recent study has shown that asymmetric dimethylarginine (ADMA) plays an important role in facilitating gastric mucosal injury by multiple factors. To explore whether the protection of rutaecarpine against gastric mucosal injury is related to reduction of ADMA content, a model of ethanol-induced gastric mucosal injury in rats was selected for this study. The ulcer index, the content of ADMA and NO, and the activity of dimethylarginine dimethylaminohydrolase (DDAH) in gastric tissues were measured in vivo after pretreatment with rutaecarpine. The in vitro effect of rutaecarpine on the release of calcitonin gene-related peptide (CGRP) and NO from isolated gastric tissues was also determined. The results showed that ethanol significantly increased the ulcer index, decreased the DDAH activity and the NO level, and elevated the ADMA level, which was attenuated by pretreatment with rutaecarpine (0.6 mg/kg or 1.2 mg/kg). In the isolated gastric tissues, rutaecarpine significantly increased the release of both CGRP and NO; the release of NO, but not CGRP, was abolished in the presence of l-NAME (10(-4) mol/L). The present results suggest that rutaecarpine protects the gastric mucosa against injury induced by ethanol and that the gastroprotection of rutaecarpine is related to reduction of ADMA levels through stimulating the release of CGRP.

Topics: Amidohydrolases; Animals; Anti-Ulcer Agents; Arginine; Calcitonin Gene-Related Peptide; Enzyme Inhibitors; Ethanol; Gastric Mucosa; Indicators and Reagents; Indole Alkaloids; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Protective Agents; Quinazolines; Rats; Rats, Sprague-Dawley; Stomach Ulcer

The aim of this study was to determine whether asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), is responsible for the detrimental effects of nicotine on ethanol-induced gastric mucosal injury and its underlying mechanisms. Gastric mucosal injury was induced by an injection of ethanol in the stomach in rats. Animals were pretreated with nicotine for 28 days before ethanol injection. The gastric mucosal ulcer index (UI) and the levels of ADMA and NO in gastric juice were determined. In vitro, the cultured mucosal epithelial cells were treated with nicotine in the presence or absence of ethanol. The concentration of ADMA in the culture medium and the ratio of cell apoptosis were measured, and the effect of nicotine or ADMA alone on cell apoptosis was also examined. In rats treated with ethanol, the UI and ADMA levels were increased and the NO level was decreased, and these effects of ethanol were augmented by pretreatment with nicotine. Administration of nicotine alone did not show significant impact on UI, ADMA level, or NO level. In vitro, incubation of human epithelial cells with ethanol induced cell injury accompanied by increased ADMA levels in the culture medium, an effect which was amplified in the presence of nicotine. Similarly, ethanol was able to induce epithelial cell apoptosis that was exacerbated by nicotine. Incubation of epithelial cells with nicotine alone did not induce cell apoptosis, but administration of ADMA alone did induce cell apoptosis. The results suggest that the gastric mucosal injury induced by ethanol is augmented by nicotine, which is related to the increased ADMA level.

Topics: Animals; Apoptosis; Arginine; Cell Culture Techniques; Cell Line; Drug Synergism; Epithelial Cells; Ethanol; Free Radical Scavengers; Gastric Juice; Gastric Mucosa; Humans; Male; Nicotine; Nitric Oxide; Random Allocation; Rats; Rats, Sprague-Dawley; Stomach Ulcer