ascorbic-acid and Stomach-Ulcer

Glucose and ascorbate used for endoscopic hemostasis metabolic preventive to prevent recurrent ulcer bleeding. Unacceptable joint use in endohemostasis ascorbate and hydrogen peroxide.

Topics: Anti-Infective Agents, Local; Antioxidants; Ascorbic Acid; Endoscopy, Gastrointestinal; Gastrointestinal Hemorrhage; Glucose; Hemostasis, Endoscopic; Humans; Hydrogen Peroxide; Stomach Ulcer; Sweetening Agents

Topics: Animals; Ascorbic Acid; Aspirin; Blood Coagulation Disorders; Buffers; Dogs; Dosage Forms; Drug Synergism; Ethanol; Gastric Juice; Gastric Mucosa; Guinea Pigs; Humans; Hydrogen-Ion Concentration; Intestinal Absorption; Leukocytes; Occult Blood; Peptic Ulcer Hemorrhage; Permeability; Rabbits; Rats; Stomach Ulcer

A series of 5-methanesulphonamido benzimidazole derivatives were designed by combining the structural features of clinically useful anti-inflammatory drugs (nimesulide and rofecoxib) and antiulcer drugs (lansoprazole, omeprazole, etc.) based on physicochemical and 3D similarity studies. The compounds were evaluated for their anti-inflammatory activity in carrageenan induced rat paw edema model taking rofecoxib and indomethacin as standard drugs. In vitro antioxidant activity of the compounds was assessed by potassium ferricyanide reducing power (PFRAP) assay. The compounds 9, 10 and 11 showed anti-inflammatory activity comparable to the standard group and were also non-ulcerogenic at the test doses. Compounds 6-11 exhibited good antioxidant effect in the concentration range (1.0-50.0µmol/ml. Preliminary theoretical ADME profiling of the compounds based on computation of selected physicochemical properties showed an excellent compliance with Lipinski's rule.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Antioxidants; Benzimidazoles; Carrageenan; Dose-Response Relationship, Drug; Edema; Molecular Structure; Rats; Stomach Ulcer; Structure-Activity Relationship; Sulfonamides

In the present study, we examined the protective effect of N,N'-dimethylthiourea (DMTU), a scavenger of hydroxyl radical (·OH), against water-immersion restraint stress (WIRS)-induced gastric mucosal lesions in rats. When male Wistar rats fasted for 24 h were exposed to WIRS for 3 h, gastric mucosal lesions occurred with increases in the levels of gastric mucosal myeloperoxidase (MPO), an index of tissue neutrophil infiltration, pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin 1beta), lipid peroxide (LPO), and nitrite/nitrate (NOx), an index of nitric oxide synthesis, and decreases in the levels of gastric mucosal nonprotein SH and vitamin C and gastric adherent mucus. DMTU (1, 2.5, or 5 mmol/kg) administered orally at 0.5 h before the onset of WIRS reduced the severity of gastric mucosal lesions with attenuation of the changes in the levels of gastric mucosal MPO, pro-inflammatory cytokines, LPO, NOx, nonprotein SH, and vitamin C and gastric adherent mucus found at 3 h after the onset of WIRS in a dose-dependent manner. Serum levels of corticosterone and glucose, which are indices of stress responses, increased in rats exposed to WIRS for 3 h, but DMTU pre-administered at any dose had no effect on these increases. These results indicate that DMTU protects against WIRS-induced gastric mucosal lesions in rats by exerting its antioxidant action including ·OH scavenging and its anti-inflammatory action without affecting the stress response.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Glucose; Corticosterone; Cytokines; Gastric Mucosa; Lipid Peroxides; Male; Neutrophil Infiltration; Nitric Oxide; Peroxidase; Protective Agents; Rats; Rats, Wistar; Stomach Ulcer; Stress, Physiological; Thiourea

3-Arylfuran-2(5H)-one derivatives show good antibacterial activity and were determined as tyrosyl-tRNA synthetase (TyrRS) inhibitors. In a systematic medicinal chemistry exploration, we demonstrated chemical opportunities to treat infections caused by Helicobacter pylori. Twenty 3-arylfuran-2(5H)-ones were synthesized and evaluated for anti-H. pylori, antioxidant and anti-urease activities which are closely interconnected with H. pylori infection. The results displayed that some of the compounds show excellent antioxidant activity, and good anti-H. pylori and urease inhibitory activities. Out of these compounds, 3-(3-methylphenyl)furan-2(5H)-one (b9) showed the most potent antioxidant activity (IC50=8.2 μM) and good anti-H. pylori activity (MIC50=2.6 μg/mL), and it can be used as a good candidate for discovering novel anti-gastric ulcer agent.

Topics: Anti-Bacterial Agents; Anti-Ulcer Agents; Antioxidants; Binding Sites; Drug Evaluation, Preclinical; Furans; Helicobacter pylori; Humans; Molecular Docking Simulation; Protein Structure, Tertiary; Stomach Ulcer; Tyrosine-tRNA Ligase; Urease

The anti-ulcerogenic potentials of low doses of rutin and cimetidine in ethanol-, acetic acid-, and stress-induced ulcers in rats have been evaluated and compared in this study. In each model, male Wistar rats were randomly divided into six groups (I-VI). Groups II-VI were administered 1 mL/100 g ethanol orally, 0.05 mL of 20% acetic acid submucosally or kept in a cold chamber for 6 h to induce ulcer in the ethanol-, acetic acid-, and stress-induced ulceration model, respectively. Thereafter, group III was post-treated with 300 mg/kg cimetidine and groups IV-VI with 20, 40, and 80 mg/kg rutin, respectively, while the control (group I) received distilled water in Tween 20. One hour after post-treatment, all groups were killed and the gastric ulcer index was calculated. Malondialdehyde (MDA) level, vitamin C content, and glutathione peroxidase (GPx) activity were evaluated in the gastric mucosa of animals. Post-treatment with rutin significantly reduced ulcerogen-induced gastric damage in all models. This effect was significant at all dose levels compared with the ulcer-induced groups. Rutin significantly reduced the MDA levels but increased the vitamin C content and GPx activity. Ulcer index and MDA level were highest in the ethanol-induced ulcer model while vitamin C content and GPx activity were lowest in the stress-induced ulcer model. The study showed that all three models of ulceration appeared to be linked to oxidative stress and also ascribed significant anti-ulcerogenic potential to rutin especially at lower doses of 20-80 mg/kg.

Topics: Animals; Anti-Ulcer Agents; Ascorbic Acid; Cimetidine; Gastric Mucosa; Glutathione Peroxidase; Male; Malondialdehyde; Rats; Rats, Wistar; Rutin; Stomach Ulcer

Naproxen (Nap) is an NSAID used as a neuroprotective agent to treat several neurodegenerative diseases. The observed limited brain bioavailability of the drug prompted the design of several chemical delivery systems. We report the synthesis and preliminary in vitro and in vivo investigations of Nap prodrugs with dihydropyridine (I) and ascorbic acid (II) through an ester spacer to target specific brain delivery of Nap. The purpose of this study was to determine the brain bioavailability of Nap after oral administration of the prodrugs in rats. The results showed moderate oral bioavailability of prodrugs (AUC = 53-94 h · μg/mL) in rats compared with parent Nap (AUC = 155 h · μg/mL) at equimolar doses. Contrarily, there was a twofold increase in Nap levels in the brain with the prodrugs compared to parent Nap. The enhanced brain bioavailability may be attributed to the specific carrier system in addition to the reduced percentage of plasma protein binding of Nap. Plasma protein binding of the tested prodrugs was investigated in vitro using equilibrium dialysis. The percentage of plasma free fraction of prodrugs (9-15%) was significantly greater than that of Nap (about 5%) when tested at 20 μM, illustrating more available prodrug to cross the blood brain barrier. A significant decrease in gastric ulcerogenicity of the prodrugs compared with parent Nap was also noted. In conclusion, oral dihydropyridine and ascorbate prodrugs for brain site-specific delivery of Nap may be promising candidates for safe, chronic use of NSAIDs for the treatment of neurodegenerative diseases.

Topics: Administration, Oral; Animals; Ascorbic Acid; Biological Availability; Blood-Brain Barrier; Brain; Dihydropyridines; Drug Design; Male; Naproxen; Neuroprotective Agents; Prodrugs; Protein Binding; Rats; Rats, Sprague-Dawley; Stomach Ulcer

We investigated the effect of Vitamin C (Vit C) on the changes of activity of the enzymes of NO-synthase system, nitric oxide content, lipoperoxidation processes, activity of SOD and catalase in gastric mucosa (GM), and concentrations of L-arginine, Vit C and Vit E in the blood of rats under conditions of experimental ulcer of the stomach caused by adrenaline injection. Vit C displayed a pronounced antioxidant action, reduced the degree of destructive affections, diminished the activity of iNOS and lipoperoxidation processes, decreased the NO content and SOD activity. Furthermore, the concentration of L-arginine and Vit C in the blood was increased. Combined action of Vit C with L-arginine reduced the degree of GM lesions, activity of eNOS and the content of NO in GM whereas the concentration of L-arginine in blood was increased. Under conditions of Vit C action and iNOS and COX-2 blockage, the activity of NO-synthases and lipoperoxidation processes were slightly decreased, indicating on dominant action of Vit C.

Topics: Animals; Antioxidants; Arginine; Ascorbic Acid; Disease Models, Animal; Gastric Mucosa; Lipid Peroxidation; Nitric Oxide; Nitric Oxide Synthase Type II; Rats; Stomach Ulcer; Superoxide Dismutase

The antiulcerogenic and antioxidant properties of Matricaria chamomilla L. (Compositae) hydroalcoholic extract (MCE) on ethanol-induced gastric mucosal injury were investigated in rats. After the induction of gastric mucosal injury, all groups were sacrificed; the gastric ulcer index was calculated, and malondialdehyde (MDA) and reduced glutathione (GSH) in whole blood and gastric tissue, and serum ascorbic acid, retinol, and beta-carotene levels were measured in all groups. Pretreatment with MCE at some doses significantly reduced gastric lesions. Again, some doses of MCE significantly reduced the MDA, and significantly increased GSH levels in gastric tissue or whole blood. Serum beta-carotene and retinol levels were significantly higher in the 200 mg/kg MCE-administered group with respect to control. As a result, MCE clearly has a protective effect against ethanol-induced gastric mucosal lesions, and this effect, at least in part, depends upon the reduction in lipid peroxidation and augmentation in antioxidant activity.

Topics: Animals; Anti-Ulcer Agents; Antioxidants; Ascorbic Acid; beta Carotene; Drug Evaluation, Preclinical; Ethanol; Glutathione; Lipid Peroxidation; Male; Malondialdehyde; Matricaria; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Stomach Ulcer; Vitamin A

Clinical supervision of successful conservative treatment of the patient with a huge stomach ulcer with use in the course of performance endoscopic a metabolic homeostasis of solutions of glucose and ascorbic acid of 5%, and also pH-chromoscopy and capillary gastrointestinal a tube is presented.

Topics: Ascorbic Acid; Endoscopy, Digestive System; Enteral Nutrition; Glucose; Hemostasis, Endoscopic; Humans; Male; Middle Aged; Peptic Ulcer Hemorrhage; Stomach Ulcer; Treatment Outcome

The aim of the present study was to evaluate if diphenyl diselenide administered by oral route was effective in restoring gastric lesions induced by ethanol. The possible involvement of oxidative stress in diphenyl diselenide antiulcer effect was also evaluated. Different doses of diphenyl diselenide (dissolved in soya bean oil, 1mL/kg) were administered orally 1h before (pre-treatment study) or 1h after ethanol (70%, v/v, 2mL/kg, post-treatment study). Ulcer lesions were quantified 1h after ethanol administration (pre-treatment protocol) or 1h after diphenyl diselenide study (post-treatment protocol). Diphenyl diselenide (0.1-10mg/kg or 0.32-32micromol/kg), when administered previously or posteriorly prevented and reversed respectively, the development of gastric lesions induced by ethanol in rats. A number of markers of oxidative stress were examined in rat stomach including thiobarbituric acid reactive species (TBARS), catalase (CAT), superoxide dismutase (SOD), non-protein thiol groups (NPSH) and ascorbic acid. In addition to attenuating the gastric lesions, low doses of diphenyl diselenide prevented (pre-treatment) or reversed (post-treatment) the ethanol-induced changes in TBARS, SOD activity and ascorbic acid content. In conclusion, the present data reveal that diphenyl diselenide, administered by oral route, possesses an antiulcer effect by modulating antioxidant mechanisms.

Topics: Animals; Anti-Ulcer Agents; Ascorbic Acid; Benzene Derivatives; Catalase; Ethanol; Intestinal Mucosa; Lipid Peroxidation; Magnetic Resonance Spectroscopy; Male; Organoselenium Compounds; Oxidative Stress; Rats; Rats, Wistar; Stomach Ulcer; Sulfhydryl Compounds; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

Reactive oxygen species (ROS) have been implicated in the etiology of indomethacin-induced gastric mucosal damage. This study investigated ascorbic acid (vitamin C)'s protective effects against oxidative gastric mucosal damage induced by indomethacin. Ascorbic acid is a powerful antioxidant because it can donate a hydrogen atom and form a relatively stable ascorbyl free radical. We have investigated alterations in the levels of myeloperoxidase, antioxidant system enzymes (glutathione S-transferase, superoxide dismutase, glutathione reductase, catalase, glutathione peroxidase), lipid peroxidation and glutathione, as markers for ulceration process following oral administration of ascorbic acid, famotidine, lansoprazole, and ranitidine in rats with indomethacin-induced ulcers. In the present study, we found that (1) ascorbic acid, famotidine, lansoprazole and ranitidine reduced the development of indomethacin-induced gastric damages; (2) the administration of indomethacin caused a significant decrease in the levels of superoxide dismutase, glutathione peroxidase, glutathione S-transferase and glutathione, and an increase in the lipid peroxidation level; (3) the administration of ascorbic acid reversed the trend, inducing a significant increase of these enzymes' levels and a reduction in lipid peroxidation level in tissues; and (4) catalase, glutathione reductase and myeloperoxidase activities, increased by indomethacin, were found to be lower in the ascorbic acid, famotidine, lansoprazole and ranitidine-treated groups. The results indicate that the gastroprotective properties of ascorbic acid could be related to its positive effects on the antioxidant system and myeloperoxidase activity in indomethacin-induced gastric ulcers in rats.

Topics: Animals; Antioxidants; Ascorbic Acid; Catalase; Gastric Mucosa; Glutathione Peroxidase; Glutathione Reductase; Indomethacin; Male; Neutrophil Infiltration; Peroxidase; Rats; Rats, Wistar; Stomach Ulcer; Superoxide Dismutase

The present study investigate the effect of ascorbic acid, the major bioactive component isolated from Cissus quadrangularis extract (CAA) on inflammatory cytokines and growth factors in non-steroidal anti-inflammatory drug (NSAID) induced gastric ulcer. Analysis of serum cytokine profile using enzymelinked immunosorbent assay (ELISA) showed a drastic increase in interleukin (IL)-1beta, IL-6, tumour necrosis factor-alpha (TNF)-alpha, interferon-gamma (IFN-gamma) and decrease in IL-10, Il-4 and prostaglandin E2 (PGE2) levels in NSAID (aspirin) treated rats. The reduction of growth factors such as transforming growth factor-alpha (TGF)-alpha and vascular endothelial cell growth factor (VEGF) by aspirin was determined by immunohistochemistry method. Administration of CAA produced significant protection against aspirin induced gastric toxicity by showing significant increase in PGE2, TGF-alpha, VEGF expression and accompanied by a significant inhibition of nitric oxide and regulating the levels of cytokines in rats. These findings suggest that CAA prevents gastric ulcer formation due to its immunomodulatory effect, antioxidant activity along with the ability to modulate PG synthesis and up-regulation of the growth factors.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; Aspirin; Cissus; Cytokines; Gastric Mucosa; Intercellular Signaling Peptides and Proteins; Male; Nitric Oxide; Rats; Rats, Wistar; Stomach Ulcer

A chronic intake of high dose alcohol may cause oxidative stress and inflammation in the stomach. It is hypothesized that cysteine-methionine and vitamin C may neutralize harmful compounds while potentiating the antioxidant capacity of the cell or tissue. The experimental animals were fed regular diets and were maintained for 90 days in the control group, the alcoholic group, which was given 2.5 g of 50% ethanol kg(-1) body wt. administered intragastrically every other day, or the alcoholic with antioxidant supplement group, to whom 2.5 g of 50% ethanol kg(-1) body wt. + a solution that contained 200 mg vitamin C, 100 mg cysteine and 100 mg methionine was administered intragastrically every other day. After the treatments, the stomach was taken for pathological and biochemical analysis. The stomach of the alcoholic group rats had higher scores of pathological findings compared with the control group, whereas the scores of the antioxidant-supplemented group were lower than the alcoholic group. In addition, the oxidized protein and lipid content in the stomachs of the alcoholic group were significantly higher than the control, but antioxidant supplementation lowered the amount of oxidation in the antioxidant supplemented group. The amount of stomach glutathione in the alcoholic group was higher than that of the control and antioxidant-supplemented groups. Interestingly, the level of total thiol in the stomach tissue of rats with antioxidant supplement was statistically higher than that of the control and alcoholic groups. In conclusion, the scores of the pathological findings in the stomach of rats with the antioxidant supplement were lower than the chronic alcohol-treated rats, albeit the amount of total thiol was increased in this group. Moreover, chronic alcohol treatment led to an increase in the level of lipid and protein oxidation in the stomach tissue of rats. A simultaneous intake of ascorbate/l-cys/l-met along with ethanol attenuated the amount of oxidation which suggested that cysteine-methionine and vitamin C could play a protective role in the stomach against oxidative damage resulting from chronic alcohol ingestion.

Topics: Acetaldehyde; Animals; Antioxidants; Ascorbic Acid; Central Nervous System Depressants; Cysteine; Ethanol; Free Radicals; Gastric Mucosa; Glutathione; Lipid Peroxidation; Methionine; Rats; Rats, Wistar; Stomach Ulcer

The study examined whether Shigyaku-san (Si-Ni-San) extract (TJ-35), a traditional Kampo medicine, prevents acute gastric mucosal lesion progression in rats treated once with compound 48/80 (C48/80). Rats treated with C48/80 (0.75 mg/kg body weight, i.p.) received TJ-35 (0.15, 0.35 or 0.75 g/kg body weight, p.o.) 0.5 h after the treatment at which time gastric mucosal lesions appeared. At 0.5 h after C48/80 treatment, the gastric mucosa of the treated rats had increased myeloperoxidase (an index of neutrophil infiltration) and xanthine oxidase activities and thiobarbituric acid reactive substances (an index of lipid peroxidation) content. At 3 h after C48/80 treatment, the gastric mucosa of the treated rats showed progressive lesions and further increases in myeloperoxidase and xanthine oxidase activities and thiobarbituric acid reactive substances content and decreases in vitamin E, ascorbic acid and adherent mucus contents and Se-glutathione peroxidase activity. Post-administered TJ-35 attenuated all these changes found at 3 h after C48/80 treatment dose-dependently. These results indicate that TJ-35 prevents the progression of C48/80-induced acute gastric mucosal lesions in rats possibly by attenuating enhanced neutrophil infiltration, enhanced lipid peroxidation associated with decreased vitamin E and ascorbic acid contents and Se-glutathione peroxidase activity, and destruction of the defensive barrier in the gastric mucosa.

Topics: Animals; Ascorbic Acid; Drugs, Chinese Herbal; Gastric Mucosa; Glutathione Peroxidase; Histamine; Male; Medicine, Kampo; Peroxidase; Plant Extracts; Rats; Rats, Wistar; Regional Blood Flow; Serotonin; Stomach Ulcer; Thiobarbituric Acid Reactive Substances; Vitamin E

The effect of oral vitamin E administration on acute gastric mucosal lesion progression was examined in rats treated once with compound 48/80 (C48/80) (0.75 mg/kg, i.p.) in comparison with that of subcutaneously administered superoxide dismutase (SOD) plus catalase (CAT). Vitamin E (50, 100 or 250 mg/kg) administered at 0.5 h after C48/80 treatment reduced progressive gastric mucosal lesions at 3 h after the treatment dose-dependently, like SOD plus CAT administered at the same time point. The gastric mucosa of C48/80-treated rats had decreased Se-glutathione peroxidase activity and vitamin E, ascorbic acid, and hexosamine contents and increased myeloperoxidase and xanthine oxidase activities and thiobarbituric acid reactive substances content at 3 h after the treatment. Administered vitamin E attenuated all these changes found at 3 h after C48/80 treatment dose-dependently, like administered SOD plus CAT. C48/80-treated rats administered with vitamin E (100 or 250 mg/kg) had higher gastric mucosal vitamin E content than C48/80-untreated rats. Neither administered vitamin E nor SOD plus CAT had any effect on the increases in serum serotonin and histamine concentrations and the decrease in gastric mucosal blood flow found at 3 h after C48/80 treatment. In the gastric mucosa of C48/80-untreated rats administered with vitamin E, thiobarbituric acid reactive substances content decreased with an increase in vitamin E content. These results indicate that orally administered vitamin E prevents acute gastric mucosal lesion progression in C48/80-treated rats possibly by suppressing oxidative stress, neutrophil infiltration, and mucus depletion in the gastric mucosa like administered SOD plus CAT.

Topics: Animals; Antioxidants; Ascorbic Acid; Catalase; Cytoplasmic Granules; Disease Progression; Dose-Response Relationship, Drug; Gastric Mucosa; Glutathione Peroxidase; Hexosamines; Histamine; Lipid Peroxidation; Male; Mast Cells; Neutrophil Infiltration; p-Methoxy-N-methylphenethylamine; Peroxidase; Rats; Rats, Wistar; Regional Blood Flow; Serotonin; Stomach Ulcer; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Vitamin E; Xanthine Oxidase

Astaxanthin (Asx), one of the carotenoids, is a red pigment in fish and Crustaceans, and possesses stronger reduction properties than conventional carotenoids, like beta-carotene. However, little is known about the biochemical properties and physiological functions of astaxanthin. The effects of astaxanthin and vitamin C on stressed rats were studied physiologically and biochemically. beta-Carotene and three kinds of astaxanthins, which were extracted from Haematococcus and Phaffia, and synthesized chemically, were used in these experiments. These rats given astaxanthins or beta-carotene had stress induced on the 12th day by immersing the rats in chest-level water at 20 degrees C for 24 h after fasting for 24 h. Rats given astaxanthins or beta-carotene prior to stressing were appreciably protected against the evolution of gastric ulcerations in relation to control rats. Ulcer indexes in particular were smaller with the rat group fed astaxanthin extracted from Haematococcus than the other groups. Next, the effects of Asx and/or vitamin C on the protection of evolution of gastric ulcer in stressed rats were persued by the same methods as described above. The results showed that rats given Asx or vitamin C were appreciably protected against the evolution of gastric ulcerations in relation to control rats. The effects were more intense, especially in rats simultaneously supplied Asx and vitamin C than in rats taking either Asx or vitamin C. It was suggested that the simultaneous supplementation of food substances with astaxanthin and vitamin C would supply enough antioxidants to offset stress-related injuries.

Topics: Alanine Transaminase; Animals; Antioxidants; Ascorbic Acid; Aspartate Aminotransferases; beta Carotene; Diet; gamma-Glutamyltransferase; Immersion; Male; Rats; Rats, Wistar; Stomach Ulcer; Stress, Physiological; Triglycerides; Xanthophylls

The interaction between Helicobacter pylori (H. pylori) and nonsteroidal anti-inflammatory drugs (NSAIDs) such as acetylsalicylic acid is still controversial. This study was designed to compare the effect of acetylsalicylic acid and vitamin C-releasing acetylsalicylic acid on the gastric mucosal damage and microbleeding before and after eradication of H. pylori in 10 young healthy volunteers. Acetylsalicylic acid induced significantly more gastric lesions and higher microbleeding than acetylsalicylic acid-vitamin C. After successful H. pylori eradication therapy, acetylsalicylic acid induced significantly higher mucosal lesions and microbleeding than before eradication. In contrast, after acetylsalicylic acid-vitamin C, gastric lesion index was significantly lower and eradication therapy failed to aggravate it. All H. pylori-positive subjects showed significant up-regulation of antioxidant enzyme (superoxide dismutase, catalase, glutathione peroxidase). Plain acetylsalicylic acid stronger than acetylsalicylic acid-vitamin C reduced gastric gene expression of these antioxidant enzymes. H. pylori eradication significantly decreased expression of these enzymes and this was further enhanced by plain acetylsalicylic acid, but not acetylsalicylic acid-vitamin C. Under plain acetylsalicylic acid therapy, the expression of proinflammatory cytokines was increased before and after eradication of H. pylori. We conclude that vitamin C combined with acetylsalicylic acid, unlike plain acetylsalicylic acid without vitamin C, protects gastric mucosa in man probably due the attenuation of oxidative stress and proinflammatory cytokines.

Topics: Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; Aspirin; Blotting, Western; Catalase; Cytokines; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Gene Expression Regulation, Enzymologic; Glutathione Peroxidase; Helicobacter Infections; Humans; Male; NF-kappa B; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Reverse Transcriptase Polymerase Chain Reaction; Stomach Ulcer; Superoxide Dismutase

We have shown earlier that restraint-cold stress-induced gastric ulceration in rats is caused by metal ion-dependent generation of hydroxyl radical (OH.) and oxidative inactivation of the gastric peroxidase (GPO), an important H2O2 scavenging enzyme. To study the mechanism of the oxidative damage of GPO, the purified enzyme was exposed to an OH. generating system containing Cu2+, ascorbate, and H2O2. Kinetic studies indicate that the enzyme is inactivated in a time-dependent process showing saturation with respect to Cu2+ concentration. The enzyme specifically requires Cu2+ and is not inactivated by the same concentration of Fe2+, Mn2+, or Zn2+. Sensitivity to catalase indicates the critical role of H2O2 in the inactivation. Inactivation is insensitive to superoxide dismutase, suggesting no role of superoxide. The rate of inactivation is not increased in D2O excluding the involvement of singlet oxygen in the process. However, OH. scavengers such as benzoate or mannitol cannot prevent inactivation. The results indicate a plausible generation of OH. within the enzyme molecule as the cause of inactivation. Fragmentation of peptide linkage or intramolecular crosslinking, gross change of tertiary structure, or change in intrinsic tryptophan fluorescence which occurs in "global" oxidation are not evident. Inactivation is dependent on pH and from a plot of K(obs) of inactivation against pH, the controlling role of an ionizable group of the enzyme having a pka of 7.8 could be suggested, deprotonation of which favors inactivation. Amino acid analysis shows a specific loss of two lysine residues in the inactivated enzyme. Competitive kinetic studies indicate that pyridoxal phosphate, a specific modifier of the lysine residue, prevents inactivation by competing with Cu2+ for binding at the GPO. A Cu2+ binding motif consisting at least of two lysine residues exists in GPO, which specifically binds Cu2+ and generates OH.. The radical oxidizes the lysine residues and perturbs the heme environment to cause inactivation. We suggest that oxidative damage of GPO is mediated by site-specific generation of OH. and not by the OH. generated in the bulk phase.

Topics: Animals; Ascorbic Acid; Cold Temperature; Copper; Free Radical Scavengers; Gastric Mucosa; Heme; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydroxyl Radical; Lysine; Oxidation-Reduction; Peroxidase; Rats; Rats, Wistar; Reactive Oxygen Species; Restraint, Physical; Stomach Ulcer; Stress, Physiological

Prevalence of peptic ulcer disease has been associated to diet. Some dietary factors seem to have bactericidal effect which may modify the risk of peptic ulcer disease. The objective was to analyze associations between dietary habits and peptic ulcers.. A cross sectional population study.. One thousand, one hundred and thirty-five subjects out of 11700 randomly invited men and women, aged 46-67 y, participating in a diet and disease study during 1991-1993. The study population comprised of 764 cases with reported peptic ulcer, 142 with dyspeptic symptoms and 229 randomly selected controls.. X-ray examinations and endoscopies were reviewed and 332 out of 764 peptic ulcer cases were verified. Mean daily intake of foods and nutrients were assessed with a combined 7d menu book and a quantitative food frequency questionnaire, including dietary supplements.. Subjects with verified ulcer had lower intake of fermented milk products and vegetables and higher intake of milk, meat and bread than controls. Intake of total fat, saturated and monounsaturated fatty acids and linolenic acid were higher in the ulcer group. Higher intake of fermented milk products, by quintiles showed a decreased ulcer risk; odds ratio 0.82 (0.71-40.95), adjusted for covariates below. Higher intake of milk, by quintiles, was associated with an increased risk of ulcer; odds ratio 1.17 (1.03-1.32). Smoking, foreign ethnicity and being unmarried or divorced were covariates associated to ulcer.. This study indicates the multifactorial etiology of peptic ulcer including dietary factors. High intake of fermented milk products was associated with decreased risk for ulcer, whereas increased risk was noted for high milk intake.

Topics: Aged; Animals; Ascorbic Acid; Cross-Sectional Studies; Diet; Dietary Carbohydrates; Dietary Fats; Duodenal Ulcer; Energy Intake; Female; Fermentation; Humans; Life Style; Male; Middle Aged; Milk; Risk Factors; Stomach Ulcer; Sweden

The aggravation of acid-induced gastric damage and its prevention by glucose, ascorbate or glutathione precursors was studied in fed and food-deprived rats. The stomachs of fed rats and those starved for 1, 3 or 5 d were vagotomized just before irrigating for 3 h with solutions containing 0-150 mmol HCI/L. Mucosal glutathione, mucus, lipid peroxides and acid back-diffusion were measured. Stomach ulcers were evaluated by morphological and histological examination. The preventive effects of glucose, ascorbate and a mixture of L-glutamine, L-glycine and L-cysteine were evaluated in the stomachs of rats that were starved for 5 d, vagotomized, then perfused for 3 h with 100 mmol HCI/L. Greater acid back-diffusion and ulcer formation, and lower glutathione and mucus levels in starved rats were dependent on the duration of starvation and luminal acidity. Increased acid back-diffusion and decreased glutathione and mucus production were negatively correlated (r < -0.80, P < 0.05) with ulcer formation. A significant enhancement in mucosal lipid peroxide concentration and serious damage of forestomach and corpus mucosal cells were observed in starved rats exposed to 100 mmol HCI/L. These ulcerogenic factors were effectively inhibited in acid-perfused stomachs of food-deprived rats by daily intraperitoneal injection of the amino acid mixture (150 mg/kg) or by an average daily consumption via drinking water of glucose (10 g) or ascorbate (1.2 g). Starvation aggravated acid-induced gastric damage and was associated with greater acid back-diffusion and oxygen radical generation, and lower mucosal glutathione and mucus production.

Topics: Amino Acids; Animals; Ascorbic Acid; Gastric Acid; Gastric Mucosa; Glucose; Glutathione; Hydrochloric Acid; Lipid Peroxides; Male; Rats; Rats, Sprague-Dawley; Starvation; Stomach Ulcer; Vagotomy

We developed a new gastric ulcer model in which the ulcers are induced by the local injection of a ferrous iron and ascorbic acid (Fe/ASA) solution into the gastric wall. These ulcers resemble human gastric ulcers that penetrate the muscularis mucosa. The involvement of oxygen radical-mediated lipid peroxidation as the cause of these ulcers was investigated. With ferrous iron or ascorbic acid alone, gastric ulcers did not form, whereas penetrating ulcers were produced by the simultaneous injection of the Fe/ASA solution in a dose-dependent manner. Lipid peroxides significantly accumulated in the gastric mucosa from 1 to 24 h after the injection of the Fe/ASA solution. This increase in lipid peroxides preceded grossly evident gastric ulcer. Treatment with superoxide dismutase (SOD, recombinant human CuZnSOD) significantly reduced the size of the ulcers and inhibited the accumulation in lipid peroxides in the gastric mucosa, while treatment with apo-SOD or heat-inactivated SOD did not. These results suggest that lipid peroxidation mediated by oxygen radicals plays a crucial role in the pathogenesis of the gastric ulceration induced by the Fe/ASA solution.

Topics: Animals; Ascorbic Acid; Disease Models, Animal; Dose-Response Relationship, Drug; Ferrous Compounds; Gastric Mucosa; Injections; Lipid Peroxides; Male; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

It has been established that prophylactic oral administration of the new derivative of n-3 polyunsaturated fatty acids--P-55 in a daily dose of 0.2 g/kg during 30 days prevents some morphological and physiological manifestations of the chronic stress-syndrome in white rats. There were normalized body and some internal organs weights, content and distribution of ascorbic acid in the adrenal tissue; decreased intensity of gastric ulcerogenesis. The behaviour of animals became more quiet. It is concluded that the preparation P-55 has a stress-protective effect during its prophylactic administration.

Topics: Animals; Ascorbic Acid; Body Weight; Chronic Disease; Drug Evaluation, Preclinical; Fatty Acids, Omega-3; Histocytochemistry; Male; Organ Size; Rats; Rats, Wistar; Sleep Deprivation; Stomach Ulcer; Stress, Physiological

Fasting gastric juice pH and concentrations of vitamin C in gastric aspirate and plasma were measured in 73 patients undergoing endoscopy. Vitamin C concentrations were significantly lower in those with hypochlorhydria (pH greater than 4; n = 23) compared with those with pH less than or equal to 4 (p less than 0.005) and there was a significant correlation between gastric juice and plasma concentrations (p = 0.002). Patients with normal endoscopic findings had significantly higher intragastric concentrations of vitamin C than those with gastric cancer (p less than 0.001), pernicious anaemia (p less than 0.005), gastric ulcer (p less than 0.01), duodenal ulcer (p less than 0.05), or after gastric surgery (p less than 0.01). There was a strong trend (0.05 less than p less than 0.1) towards lower intragastric concentrations of vitamin C in patients with chronic atrophic gastritis. In vitro, vitamin C concentrations remained stable in acidic but fell significantly over 24 hours in alkaline gastric aspirate. Gastric secretory studies in five volunteers showed that vitamin C concentrations increased significantly after intramuscular pentagastrin. These findings suggest that the low fasting levels of vitamin C in hypochlorhydric gastric juice may be caused by chemical instability and that vitamin C may be secreted by the human stomach.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Pernicious; Ascorbic Acid; Diet; Duodenal Ulcer; Female; Gastrectomy; Gastric Acidity Determination; Gastric Juice; Humans; Male; Middle Aged; Stomach Diseases; Stomach Neoplasms; Stomach Ulcer

Levels of certain metabolites of peroxidation of lipids such as diene conjugates malonic dialdehyde, ascorbic acid, dehydroascorbic acid and diketogulonic acid were compared in 39 cases of gastric ulcer, 25 patients with gastric cancer and 14 healthy subjects. Diene conjugates and malonic dialdehyde levels appeared to be increased in cases of gastric ulcer and cancer. This was matched by a decrease in ascorbic acid and dehydroascorbic acid levels. Ulcer patients revealed enhanced diketogulonic acid concentration.

Topics: 2,3-Diketogulonic Acid; Adenocarcinoma; Aged; Ascorbic Acid; Dehydroascorbic Acid; Female; Humans; Lipid Peroxides; Male; Malondialdehyde; Middle Aged; Stomach Neoplasms; Stomach Ulcer

Topics: Adolescent; Adult; Aged; Ascorbic Acid; Female; Gastrectomy; Gastric Juice; Humans; Male; Middle Aged; Nitrites; Nitroso Compounds; Stomach Ulcer; Vagotomy

Topics: Animals; Ascorbic Acid; Aspirin; Copper; Drug Combinations; Female; Ferrous Compounds; Gastric Juice; Humans; Iron; Male; Rats; Stomach Ulcer; Stress, Psychological

Rats were orally administered 1-ascorbic acid, nicotine 1-ascorbic acid and nicotine, or distilled water for 10 days. Following this treatment they were fasted for 24 h and then restrained in a cold environment for 2 h. Nicotine alone produced significantly more gastric ulcers than any other treatment. 1-Ascorbic acid increased ulceration relative to controls. The combined effects of 1-ascorbic acid and nicotine resulted in reduced ulcer incidence and severity. It appears that l-ascorbic acid and nicotine do not act synergistically to augment stress-induced gastric ulcer.

Topics: Animals; Ascorbic Acid; Cold Temperature; Drug Synergism; Fasting; Male; Nicotine; Rats; Rats, Inbred Strains; Restraint, Physical; Stomach Ulcer; Stress, Physiological

Ascorbic acid and ferrous sulfate were given to peptic ulcer patients (C-Fe therapy). In gastric ulcer patients, the healing index of the C-Fe therapy group was significantly higher than that of controls, but in duodenal ulcer patients, no significant difference was observed between the healing index of the C-Fe therapy group and that of controls. According to these results, it was concluded that C-Fe therapy was effective in healing gastric ulcers and that the cause of duodenal ulcers might depend more on aggressive factors than that of gastric ulcers.

Topics: Adult; Aged; Ascorbic Acid; Drug Evaluation; Drug Therapy, Combination; Duodenal Ulcer; Ferrous Compounds; Humans; Iron; Middle Aged; Stomach Ulcer

Rats were orally administered ascorbic acid at a dose of 30 g/liter during either total starvation, partial starvation, the activity-stress ulcer procedure, or the restraint-cold procedure. In four experiments, ascorbic acid failed to exert significant protective action against stomach ulcer formation and, in fact, may have potentiated the ulcerogenic process.

Topics: Animals; Ascorbic Acid; Cold Temperature; Dose-Response Relationship, Drug; Male; Physical Exertion; Rats; Restraint, Physical; Starvation; Stomach; Stomach Ulcer; Stress, Physiological

Blood was obtained from 11 healthy voluteers, mixed with two standard types of anticoagulant used in blood transfusion centres and stored for 21-28 days at 4 degrees C. Leucocyte ascorbic acid (LAA) fell to deficient levels after 7 days in all cases. There were no corresponding changes in plasma ascorbic acid (PAA) levels. LAA and PAA were measured before, during and after surgery in 5 control patients who underwent definitive operations for benign peptic ulceration and in 4 patients under-going surgery for bleeding peptic ulceration. The average amount of blood administered to the latter group was 10 units. There was a fall in LAA and PAA in both groups of patients after operation. This fall had returned to normal by 7 days in the controls, but the LAA remained at a deficient level at 7 days in the patients who had bled. Deficient ascorbic acid in stored blood may contribute to low leucocyte ascorbic acid levels in patients after blood transfusion and may contribute to the increased complication rate when surgery is undertaken in these patients.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Preservation; Female; Humans; Leukocytes; Male; Peptic Ulcer; Peptic Ulcer Hemorrhage; Stomach Ulcer; Transfusion Reaction

Topics: Administration, Oral; Animals; Ascorbic Acid; Body Weight; Female; Gastric Mucosa; Rats; Starvation; Stomach; Stomach Ulcer; Time Factors

Topics: Ascorbic Acid; Female; Humans; Male; Niacinamide; Postgastrectomy Syndromes; Stomach Ulcer; Vitamin B Complex; Vitamin D; Vitamin K; Vitamins

Topics: Animals; Ascorbic Acid; Deoxyglucose; Gastric Acidity Determination; Gastric Mucosa; Male; Rats; Stomach; Stomach Ulcer

Topics: Animals; Ascorbic Acid; Catecholamines; Dihydroxyphenylalanine; Gastric Mucosa; Rats; Stomach Ulcer

Topics: Adolescent; Adult; Aged; Ascorbic Acid; Chronic Disease; Duodenal Ulcer; Female; Humans; Male; Middle Aged; Stomach Ulcer

Topics: Animals; Ascorbic Acid; Female; Glucose; Injections, Intraperitoneal; Male; Rats; Stomach Ulcer; Time Factors

Topics: Adrenal Glands; Animals; Ascorbic Acid; Cold Temperature; Gastric Acidity Determination; Gastric Juice; Hot Temperature; Humidity; Noise; Seasons; Stomach Diseases; Stomach Ulcer; Stress, Physiological; Swine; Swine Diseases; Temperature

Topics: Anti-Inflammatory Agents; Ascorbic Acid; Humans; Iron; Stomach Ulcer

Topics: Adaptation, Psychological; Adrenal Glands; Analysis of Variance; Animals; Ascorbic Acid; Electroshock; Fear; Food Deprivation; Humans; Male; Rats; Reflex, Startle; Stomach Ulcer; Stress, Psychological; Time Factors; Water Deprivation

Topics: Animal Feed; Animals; Ascorbic Acid; Esophageal Diseases; Female; Male; Stomach Ulcer; Temperature; Ulcer; Zea mays

Topics: Amines; Aminopyrine; Animals; Ascorbic Acid; Aspirin; Chlorpromazine; Cortisone; Desoxycorticosterone; Diphenhydramine; Female; Indomethacin; Male; Phenylbutazone; Prednisone; Procaine; Quaternary Ammonium Compounds; Rats; Reserpine; Stomach Ulcer; Tetracaine

Topics: Animal Feed; Animals; Ascorbic Acid; Breeding; Stomach Ulcer; Swine; Swine Diseases; Vitamin B Complex; Zea mays

Topics: Adrenal Glands; Animals; Appetite; Ascorbic Acid; Body Weight; Consummatory Behavior; Humans; Physiology; Rats; Research; Stomach Ulcer; Stress, Physiological

Topics: Ascorbic Acid; Atropa belladonna; Bicarbonates; Diet; Diet Therapy; Gastrointestinal Tract; Humans; Milk; Phenobarbital; Smoking; Stomach Ulcer; Terpenes; Tissue Extracts

Topics: Animals; Ascorbic Acid; Flavonoids; Guinea Pigs; Hesperidin; Histamine; Histamine Agents; Humans; Peptic Ulcer; Stomach Ulcer; Vitamins

Topics: Ascorbic Acid; Hospitalization; Humans; Peptic Ulcer; Phenobarbital; Stomach Ulcer; Wound Healing