allopurinol and Gastritis

The aim of this study was to test the effect of antioxidant supplementation on enzymatic abnormalities and free radical-modified DNA adducts associated with premalignant changes in the gastric mucosa of elderly patients with HP-negative atrophic gastritis (CAG). Sixty patients with atrophic gastritis and intestinal metaplasia underwent a nutritional interview and a gastroscopy with multiple biopsy samples in the antrum that were processed for histology and for assaying: alpha-tocopherol, MDA, xanthine oxidase (XO), ornithine decarboxylase (ODC), and 8-OHdG. Patients were randomly allocated into three matched groups and supplemented for 6 months with (1) vitamin E, 300 mg/day; (2) multivitamin, two tablets t.i.d.; and (3) Immun-Age 6 g/day nocte (ORI, Gifu, Japan), a certified fermented papaya preparation with basic science-validated antioxidant/immunomodulant properties. Ten dyspeptic patients served as controls. Histology and biochemistry were blindly repeated at 3 and 6 months. CAG patients showed a significantly (P <.05) increased level of mucosal MDA and XO concentration that were reverted to normal by each supplementation (P <.05). All supplements caused a significant decrease of ODC (P <.01), but Immun-Age yielded the most effective (P < 0.05) and was the only one significantly decreasing 8-OhdG (P < 0.05). These data suggest that antioxidant supplementation, and, namely, Immun-Age, might be potential chemopreventive agents in HP-eradicated CAG patients and especially in the elderly population.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aging; Antioxidants; Deoxyguanosine; Dietary Supplements; DNA; DNA Adducts; Gastric Mucosa; Gastritis; Gastritis, Atrophic; Gene Expression Regulation; Humans; Models, Biological; Mucous Membrane; Oxidants; Oxidative Stress; Pilot Projects; Precancerous Conditions; Random Allocation; Reverse Transcriptase Polymerase Chain Reaction; Stomach Neoplasms; Up-Regulation; Vitamin E; Vitamins; Xanthine Oxidase

The effect of the free radical scavengers allopurinol (50 milligrams) and dimethyl sulfoxide (DMSO) (500 milligrams), taken orally four times a day, on the clinical outcome of hematemesis resulting from nonsteroidal anti-inflammatory drugs (NSAID) induced erosive gastritis was examined in a prospective randomized double-blinded controlled trial. In 180 fully evaluable patients with osteoarthritis or rheumatoid arthritis, administration of allopurinol (n = 63) or DMSO (n = 58) enabled significantly (p < 0.01) larger numbers of patients to remain hemodynamically stable with no rebleed relative to those in the control group (n = 59). The results of endoscopic examination 48 hours after admission demonstrated that gastric erosions were still present in significantly more patients in the control group (p < 0.01; n = 20; 50 percent) than in the allopurinol (n = 5; 9 percent) or DMSO (n = 4; 7 percent) groups. The radical scavengers also reduced the number of patients requiring blood transfusion because of a rebleed or continued bleeding and emergency operation relative to control values. It is, thus, construed that oxygen derived free radicals mediate the mechanism of NSAID induced erosive gastritis. Scavenging these radicals impairs the gastritis, stimulates healing and protects against the complications of its hemorrhagic episodes.

Topics: Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Dimethyl Sulfoxide; Double-Blind Method; Female; Free Radical Scavengers; Gastritis; Hematemesis; Humans; Male; Middle Aged; Osteoarthritis; Prospective Studies; Treatment Outcome

Topics: Allopurinol; Drug Hypersensitivity; Gastritis; Gout; Gout Suppressants; Humans; Male; Middle Aged; Probenecid; Uric Acid; Uricosuric Agents

Rebamipide, a gastroprotective drug, was developed in Japan and was proven to be superior to cetraxate, the former most prescribed drug of the same category, in 1989 in the treatment for gastric ulcers. The initially discovered basic mechanisms of action of rebamipide included its action as a prostaglandin inducer and oxygen free-radical scavenger. In the last 5 years, several basic and clinical studies have been performed for functional dyspepsia, chronic gastritis, NSAID-induced gastrointestinal injuries, gastric ulcer following eradication therapy for Helicobacter pylori, gastric ulcer after endoscopic surgery and ulcerative colitis. In addition, several molecules have been identified as therapeutic targets of rebamipide to explain its pleiotropic pharmacological actions. The aim of this article is to provide an update on the pharmacological and clinical profile of rebamipide and to explore further possibilities for additional indications.

Topics: Adult; Aged; Aged, 80 and over; Alanine; Alendronate; Allopurinol; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Drug Interactions; Gastritis; Helicobacter Infections; Humans; Male; Mice; Quinolones; Randomized Controlled Trials as Topic; Rats; Stomach Ulcer

We examined the recurrence of gastric mucosal lesions in rats after a single treatment with compound 48/80 (C48/80), a mast cell degranulator. During the period of 0.5 h to 24 h after treatment with C 48/80 (0.75 mg/kg, i.p.), an apparent recurrence of gastric mucosal lesions was found 18 and 24 h after the lesion formation, progression, and recovery occurred during the period of 12 h. Gastric mucosal blood flow showed the maximum reduction at 0.5, 16, and 22 h after treatment followed by the maximum recovery of the decrease at 12, 20, and 24 h, respectively. Gastric mucosal myeloperoxide and xanthine oxidase activities and lipid peroxide content showed the maximum increase at 3, 18, and 24 h after treatment. Gastric mucosal superoxide dismutase activity unchanged after treatment and gastric mucosal catalase activity decreased only at 24 h. Gastric mucosal Se-glutathione peroxidase activity and vitamin E, ascorbic acid, and hexosamine contents showed their maximum decrease at 3, 18, and 24 h after treatment. Gastric mucosal non-protein SH content showed the maximum decrease at 0.5, 16, and 22 h after treatment. Serum histamine and serotonin concentrations increased rapidly after treatment but the increases in serum histamine and serotonin concentrations diminished completely until 12 and 14 h, respectively. These results indicate that lesions recur repeatedly accompanied with an ischemia-reperfusion-like change in blood flow, inflammation, and disruption of antioxidant defense systems in the gastric mucosa of rats in no relation to released histamine and serotonin after a single C48/80 treatment.

Topics: Animals; Ascorbic Acid; Autacoids; Catalase; Cell Degranulation; Gastric Mucosa; Gastritis; Glutathione Peroxidase; Hexosamines; Lipid Peroxides; Male; Mast Cells; p-Methoxy-N-methylphenethylamine; Peroxidase; Rats; Rats, Wistar; Recurrence; Regional Blood Flow; Severity of Illness Index; Sulfhydryl Compounds; Time Factors; Vitamin E; Xanthine Oxidase

In this experimental study, the role of free oxygen radicals (FOR) in stress gastritis (SG) was investigated in a restraint stress model for rats. Allopurinol, dimethyl sulfoxide (DMSO), and superoxide dismutase (SOD) were tested as single agents in controlled groups. The portal blood pH values, the ratio of the mucosal erosion area to the gastric mucosal area (EA/MA), the ratio of the depth of mucosal erosions to the concomitant gastric mucosal wall (ED/MD), and concentrations of malondialdehyde (MDA)--a lipid peroxidation coproduct--in the gastric mucosa were used as parameters in the experiment. The EA/MA between the treated and untreated control groups were found to have no statistically significant difference (P > 0.05). ED/MD, a crucial determinant for bleeding probability, was found to be decreased in the SOD group (P < 0.05). SOD, allopurinol, and DMSO reduced the mucosal MDA concentration to lower values than the untreated group (P < 0.05). We concluded that although FOR may not play a dominant role in stress-induced gastric lesions, SOD may be a good candidate for a clinical trial on SG prophylaxis.

Topics: Allopurinol; Animals; Dimethyl Sulfoxide; Free Radical Scavengers; Free Radicals; Gastritis; Male; Oxygen; Rats; Rats, Wistar; Restraint, Physical; Stress, Physiological; Superoxide Dismutase

Oxygen-derived free radicals are cytotoxic and produce tissue damage. The effect of the radical scavengers allopurinol and dimethyl sulfoxide (DMSO) on aspirin- and ethanol-induced acute gastric mucosal injury was studied in the rat. Orogastric instillation of aspirin at 200 mg/kg produced, after 4 h, gastric mucosal injury in 30% of rats without pyloric ligation [score, 3.1 +/- 0.8 mm2, mean +/- standard error of the mean (SEM); n = 10] and in 80% of rats with this ligation (score, 10.4 +/- 1.2 mm2, mean +/- SEM; n = 10). Gavage with 1 mL of 2 or 5% allopurinol or DMSO at 24 h before and again just before aspirin administration completely protected rats with or without pyloric ligation against injury. Orogastric instillation of ethanol (1 mL of a 40% solution) produced, after 1 h, gastric mucosal injury in all rats with or without pyloric ligation (24.1 +/- 1.7 and 14.1 +/- 1.3 mm2, respectively, mean +/- SEM; n = 10). Gavage with 1 mL of 5% allopurinol or DMSO at 24 h before and again just before ethanol administration completely protected rats with or without pyloric ligation against injury. Protection against the aspirin- and ethanol-induced injury was not associated with any significant effect on the H+ output. The results suggest that oxygen-derived free radicals are directly implicated in the mechanism of aspirin- and ethanol-induced acute gastric mucosal injury and that scavenging these free radicals protects against injury by maintaining the integrity of the gastric mucosa.

Topics: Allopurinol; Animals; Aspirin; Dimethyl Sulfoxide; Ethanol; Female; Free Radical Scavengers; Gastritis; Male; Rats; Rats, Inbred Strains

Stress gastritis frequently occurs in association with shock or sepsis. Gastric mucosal ischemia appears to be a key feature in these critically ill patients. The University of Wisconsin cold preservation solution (UWS) is an isoosmolar, nonglucose-based perfusate that minimizes hypothermia-induced cell swelling and prevents intracellular acidosis and oxygen-free radical injury, while providing high energy substrates for donor organs. In a prospective, single-blind study, 18 similar Sprague-Dawley rats were randomly divided to receive only 5 per cent dextrose and water (D5W) (Group 1) or a 50 per cent solution of D5W+UWS (Group 2) for 72 hours. At the end of 72 hours the animals were stressed by the cold-restraint model. The mean number of ulcers for Group 2 was nearly half that of Group 1. Also, Group 2 had a significantly lower mean total ulcer length (P less than 0.005) and ulcer index (P less than 0.05). Most of Group 2 had mild gastritis changes (grade 0 to 1), while more than half of Group 1 had severe gastritis (grade 3). Gastric mucosal pH was similar for both groups. Topically applied UWS appears to reduce the severity and incidence of stress gastritis in this experimental model. Because mucosal pH values were similar, it is thought that UWS may alter the effects of gastric mucosal ischemia at a cellular level.

Topics: Adenosine; Administration, Oral; Allopurinol; Animals; Cardioplegic Solutions; Gastric Mucosa; Gastritis; Gastrointestinal Hemorrhage; Glucose; Glutathione; Hydrogen-Ion Concentration; Insulin; Male; Organ Preservation Solutions; Prospective Studies; Raffinose; Rats; Rats, Inbred Strains; Single-Blind Method; Solutions; Stomach Ulcer; Stress, Physiological; Tissue Preservation

The effect of the radical removing agents, allopurinol and dimethyl sulphoxide (DMSO), on the healing rate of ethanol (1 ml of 40% solution) induced gastric mucosal injury was studied in the rat. One millilitre of 1, 2 or 5% allopurinol or DMSO were instilled into the stomach 1, 24 and 48 h after giving ethanol by gavage. One hour after administration of ethanol, gastric mucosal injury was produced in all animals (20.4 +/- 1.2 mm2, mean +/- SEM, n = 10). Treatment for 24 h with 2% allopurinol or DMSO significantly (p less than 0.01) reduced the extent of the ethanol injury (11.1 +/- 0.8 and 11.9 +/- 0.9 mm2, respectively, vs. 19.2 +/- 1.1 mm2, n = 10) and this was similarly achieved by the 5% solutions (10.4 +/- 0.9 and 10.2 +/- 0.8 mm2, respectively, vs. 19.2 +/- 1.1 mm2, n = 10). After treatment for 48 h, 30% of animals having 1% allopurinol or DMSO remained with injury significantly (p less than 0.001) less than that seen with ethanol alone (4.1 +/- 0.4 and 3.9 +/- 0.5 mm2, respectively, vs. 12.1 +/- 0.9 mm2, n = 10); however, none treated with 2 or 5% solutions remained with any injury. Healing of this injury was confirmed microscopically and was achieved by regeneration. Thus, removing oxygen-derived free radicals stimulates the healing of ethanol-induced acute gastric mucosal injury in the rat.

Topics: Allopurinol; Animals; Dimethyl Sulfoxide; Ethanol; Female; Free Radical Scavengers; Free Radicals; Gastritis; Male; Oxygen; Rats; Rats, Inbred Strains; Wound Healing

Topics: Adult; Aged; Albuminuria; Allopurinol; Benzothiadiazines; Diuretics; Drug Hypersensitivity; Drug Interactions; Fever; Gastritis; Gastrointestinal Hemorrhage; Glomerulonephritis; Gout; Hematuria; Humans; Kidney; Male; Sodium Chloride Symporter Inhibitors