allopurinol and Stomach-Ulcer

Topics: Animals; Cats; Dimethyl Sulfoxide; Disease Models, Animal; Ethanol; Gastric Mucosa; Ischemia; Lipid Peroxides; Neutrophils; Rats; Stomach Ulcer; Sulfhydryl Compounds; Superoxide Dismutase; Xanthine Oxidase

Topics: Adult; Allopurinol; Dimethyl Sulfoxide; Female; Free Radicals; Gastric Mucosa; Humans; Hydroxides; Hydroxyl Radical; Male; Middle Aged; Prospective Studies; Randomized Controlled Trials as Topic; Stomach Ulcer; Stress, Physiological; Superoxides

To investigate the gastroprotective effects of Acanthopanax senticosus leaves (ASLs) extrusion on acute gastric mucosal lesion in rats induced by compound 48/80 (C48/80).. Rats were divided into six groups: normal; C48/80-induced gastric lesion control; gastric lesion positive control (famotidine 4 mg/kg); gastric lesion administered with two levels of extruded ASLs (ASLE, 40 and 200 mg/kg); and gastric lesion treated with ASLs (ASL 200 mg/kg). Mucus secretion/damage was determined by immunohistological staining. Immunofluorescence and western blotting were performed to determine gastric mucosal Bax and Bcl-2 expression. Gastric mucosal oxidative-stress-related enzymes and malondialdehvde were determined.. C48/80-induced mucus depletion and inflammation in the gastric mucosa were significantly attenuated by ASLs. The increased serum serotonin and histamine concentrations in C48/80-treated rats were also attenuated by ASLs. Gastric mucosal Bax protein expression was increased and Bcl-2 expression was decreased after C48/80 treatment, and ASLs ameliorated Bax and Bcl-2 expression. The extrusion process significantly augmented the effects of ASLs in a dose-dependent manner. ASLEs at 200 mg/kg normalized mucus damage/secretion, C48/80-induced increases of mucosal myeloperoxidase activity (index of inflammation), xanthine oxidase, and malondialdehyde content (index of lipid peroxidation). The effects of ASLs on Bax and Bcl-2 expression were also enhanced by extrusion. Furthermore, these effects of ASLEs at 200 mg/kg were similar to those of famotidine, a histamine H2-receptor antagonist commonly used to treat gastric ulcers.. ASLEs prevented acute gastric mucosal lesion progression induced by C48/80, possibly by inducing mucus production, and reduced inflammation and oxidative stress in gastric mucosa through an anti-apoptotic mechanism.

Topics: Animals; Drug Synergism; Drug Therapy, Combination; Drugs, Chinese Herbal; Eleutherococcus; Gastric Mucosa; Glutathione Peroxidase; Histamine; Humans; Male; Malondialdehyde; p-Methoxy-N-methylphenethylamine; Plant Leaves; Rats; Rats, Wistar; Stomach Ulcer; Xanthine Oxidase

In traditional medicine, the leaves, flowers, barks and roots of Muntingia calabura L. (Muntingiaceae) have been employed as a treatment for various ailments including dyspepsia and to relieve pain caused by gastritis and peptic ulcer disease. The methanolic extract of Muntingia calabura leaves (MEMC) has been proven in the previous study to possess significant antiulcer activity. In this study, we attempted to determine the prophylactic effect of the fractions obtained from MEMC against ethanol-induced gastric lesion in rats and the involvement of antioxidants and anti-inflammatory mediators.. The MEMC was fractionated with petroleum ether (PEF), ethyl acetate (EAF) and distilled water (AQF). These fractions were investigated for possible antiulcer property using ethanol-induced gastric ulcer rat model. The rats were administered orally once daily with 8% Tween 80 (control), 100mg/kg ranitidine, or the fractions, in the doses of 100, 250, and 500 mg/kg, for 7 days, followed by ulcer induction using absolute ethanol. The rats were euthanized; macroscopic and histological observations of the stomach were done. The ulcer area (UA) was determined and the percentage protection afforded by the fractions was calculated. The fractions were subjected to antioxidant studies including the superoxide and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, oxygen radical absorbance capacity (ORAC) and total phenolic content (TPC) assay. Involvement of nitric oxide (NO) and inflammatory mediators such as lipoxygenase (LOX) and xanthine oxidase (XO) were evaluated. Phytochemical screening and HPLC analysis of the fractions were also conducted.. Pre-treatment of PEF and EAF significantly (p<0.001) attenuated the gastric lesions as compared to the control group in a dose-dependent manner. On the other hand, 100 and 250 mg/kg of AQF significantly (p<0.001) prevented the ulcer formation but at the highest dose (500 mg/kg), AQF failed to significantly reduce the ulcer formation, showing a dose-independent antiulcerative effect of AQF. The histological evaluation supported the observed gastroprotective activity of PEF, EAF and AQF. All the fractions showed high superoxide and DPPH scavenging activity, meanwhile the EAF showed highest TPC followed by PEF and AQF. These fractions also significantly (p<0.05) inhibited the NO while maintaining the viability of the cells. EAF exhibited high inhibition towards both the LOX and XO enzymes, meanwhile PEF and AQF exerted high LOX inhibition but low XO inhibition. Phytochemical screening and HPLC profiling suggested the presence of flavonoid- and tannin based compounds in PEF and EAF.. It can be concluded that the prophylactic effect of the fractions on gastric ulceration in rats is associated with its high antioxidant activity and its ability to effectively inhibit the inflammation mediators. Presence of several flavonoids and gallic acid explains the effectiveness of the fractions in affording protection against gastric damages.

Topics: Animals; Anti-Inflammatory Agents; Anti-Ulcer Agents; Antioxidants; Biphenyl Compounds; Cell Line; Cell Survival; Ethanol; Magnoliopsida; Male; Methanol; Mice; Nitrites; Phytotherapy; Picrates; Plant Extracts; Plant Leaves; Rats, Sprague-Dawley; Solvents; Stomach Ulcer; Superoxides; Xanthine Oxidase

Muntingia calabura L. (Muntingiaceae) is locally known as kerukup siam. Its leaves, flowers, barks and roots have been used traditionally in East Asia and South America to treat various diseases including ulcer-related diseases. The present study aimed to investigate the mechanism(s) of gastroprotective effect of methanol extract of Muntingia calabura leaves (MEMC) using the pylorus ligation induced gastric ulceration in rats.. Five groups of rats (n=6) were administered orally once daily for 7 days with 8% Tween 80 (negative control), 100 mg/kg ranitidine (positive control), or MEMC (100, 250 or 500 mg/kg), followed by the ulcer induction via ligation of the pyloric part of the rat's stomach. This was followed by the macroscopic analysis of the stomach, evaluation of gastric content parameters, and quantification of mucus content. The antioxidant (measured using the superoxide anion and 2,2-diphenyl-1-picrylhydrazyl (DPPH)-radical scavenging, oxygen radical absorbance capacity (ORAC) and total phenolic content (TPC) assays), anti-inflammatory (evaluated using the in vitro lipoxygenase and xanthine oxidase assays), phytoconstituents and HPLC analysis of MEMC were also carried out.. The MEMC significantly (p<0.05) reduced gastric lesion in this model. Furthermore, the extract also significantly (p<0.01) reduced the volume of gastric content whereas the total acidity was significantly (p<0.05) reduced in the doses of 100 and 500 mg/kg MEMC. Moreover, the mucus content increased significantly (p<0.01) in MEMC-treated rats. The extract also showed high antioxidant and anti-inflammatory activities in all assays tested, and demonstrated the presence of high tannins and saponins followed by flavonoids.. The MEMC exerted gastroprotective effect via several mechanisms including the anti-secretory, antioxidant and anti-inflammatory activities. These activities could be attributed to the presence of tannins, saponins and flavonoids (e.g. rutin, quercitrin, fisetin and dihydroquercetin).

Topics: Animals; Anti-Ulcer Agents; Antioxidants; Cell Line; Cell Survival; Chromatography, High Pressure Liquid; Gastric Juice; Lipoxygenase; Male; Mice; Nitric Oxide; Phytochemicals; Plant Extracts; Plant Leaves; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Tracheophyta; Xanthine Oxidase

Jatropha isabellei Müll Arg. (Euphorbiaceae) is a medicinal plant that has been used in South American folk medicine for the treatment of arthritic diseases, particularly gout.. This study was designed to verify the antinociceptive, anti-inflammatory and hypouricemic potential of Jatropha isabellei.. Rats were orally administered with the crude extract (100-300 mg/kg) or a fraction that is rich in alkaloids (0.15 mg/kg) of Jatropha isabellei. An intra-articular (i.a.) injection of 50 μl of monosodium urate (MSU) crystals (1.25mg/site) was used to generate the gout model to assess the effect of the treatment on nociception (thermal and mechanical hyperalgesia) and inflammation (oedema and neutrophil infiltration). The effect of Jatropha isabellei on the serum levels of uric acid was evaluated in a model of hyperuricaemia induced by the intraperitoneal injection of potassium oxonate (250 mg/kg). The side effects were analysed using an open-field test, gastric lesion assessment and by measuring the levels of the ALT and AST enzymes.. Our study demonstrated that the crude extract of Jatropha isabellei and a fraction rich in alkaloids were able to prevent the thermal hyperalgesia, mechanical allodynia, oedema and neutrophil infiltration induced by intra-articular MSU injection in rats. On the other hand, treatment with Jatropha isabellei did not alter the uric acid levels increased by potassium oxonate in the hyperuricaemia model. In addition, Jatropha isabellei did not induce gastric lesions or liver damage and did not alter spontaneous locomotor activity.. The crude extract of Jatropha isabellei and its fraction rich in alkaloid presents antinociceptive and anti-inflammatory effects in a rat gout model, similar to that observed after treatment with colchicine, supporting the traditional use of this plant in gouty patients.

Topics: Alkaloids; Animals; Anti-Inflammatory Agents; Arthritis, Gouty; Biomarkers, Pharmacological; Disease Models, Animal; Edema; Hyperalgesia; Hyperuricemia; Jatropha; Male; Motor Activity; Neutrophil Infiltration; Oxonic Acid; Peroxidase; Phytotherapy; Plant Extracts; Rats; Stomach Ulcer; Uric Acid; Xanthine Oxidase

The aim of this study was to examine the effect of ACS14, a hydrogen sulfide (H(2)S)-releasing derivative of aspirin (Asp), on Asp-induced gastric injury. Gastric hemorrhagic lesions were induced by intragastric administration of Asp (200 mg/kg, suspended in 0.5% carboxymethyl cellulose solutions) in a volume of 1 ml/100 g body weight. ACS14 (1, 5 or 10 mg/kg) was given 30 min before the Asp administration. The total area of gastric erosions, H(2)S concentration and oxidative stress in gastric tissues were measured three hours after administration of Asp. Treatment with Asp (200 mg/kg), but not ACS14 (430 mg/kg, at equimolar doses to 200 mg/kg Asp), for 3 h significantly increased gastric mucosal injury. The damage caused by Asp was reversed by ACS14 at 1-10 mg/kg in a concentration-dependent manner. ACS14 abrogated Asp-induced upregulation of COX-2 expression, but had no effect on the reduced PGE(2) level. ACS14 reversed the decreased H(2)S concentrations and blood flow in the gastric tissue in Asp-treated rats. Moreover, ACS14 attenuated Asp-suppressed superoxide dismutase-1 (SOD-1) expression and GSH activity, suggesting that ACS14 may stimulate antioxidants in the gastric tissue. ACS14 also obviously inhibited Asp-induced upregulation of protein expression of oxidases including XOD, p47(phox) and p67(phox). In conclusion, ACS14 protects Asp induced gastric mucosal injury by inhibiting oxidative stress in the gastric tissue.

Topics: Animals; Aspirin; Cyclooxygenase 2; Delayed-Action Preparations; Dinoprostone; Disulfides; Dose-Response Relationship, Drug; Gastric Mucosa; Gene Expression Regulation; Glutathione; Hydrogen Sulfide; Male; NADPH Oxidases; Oxidative Stress; Phosphoproteins; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Superoxide Dismutase; Superoxide Dismutase-1; Xanthine Oxidase

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

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

Infection with Salmonella typhimurium can produce multiple organ dysfunctions. However, document concerning with gastric hemorrhagic ulcers occur in this infectious disease is lacking. The aim was to study modulation of gastric hemorrhagic ulcer by oxidative stress and mast cell histamine in S. typhimurium-infected rats. Additionally, the protective effects of drugs, such as ofloxacin, lysozyme chloride, ketotifen, ranitidine, and several antioxidants, including exogenous glutathione (GSH), allopurinol and dimethylsulfoxide (DMSO) were evaluated. Male Wistar rats were injected intrajejunally with a live culture of S. typhimurium (1 x 10(10) colony-forming units/rat) and followed by deprivation of food for 36 h. Age-matched control rats received sterilized vehicle only. Rat stomachs were irrigated for 3 h with either normal saline or a simulated gastric juice containing 100 mM HCl, 17.4 mM pepsin and 54 mM NaCl. S. typhimurium caused aggravation of offensive factors, including enhancing gastric acid back-diffusion, mucosal lipid peroxide generation, histamine release, microvascular permeability and hemorrhagic ulcer, as well as an attenuation of defensive substances, such as mucosal GSH and mucus level. Intragastric irrigation of gastric juice caused further aggravation of these gastric biochemical parameters. This exacerbation of ulcerogenic factors was abolished by pretreatment of ofloxacin and lysozyme chloride. Antioxidants, such as reduced GSH, allopurinol and DMSO also produced significant (P < 0.05) amelioration of gastric damage in S. typhimurium infected rats. In conclusion, gastric oxidative stress and histamine play pivotal roles in the formation of hemorrhagic ulcers that were effectively ameliorated by ofloxacin, lysozyme chloride, ketotifen, ranitidine, diamine oxidase and various antioxidants in S. typhimurium-infected rats.

Topics: Allopurinol; Animals; Antioxidants; Dimethyl Sulfoxide; Disease Models, Animal; Gastric Juice; Gastric Mucosa; Gastrointestinal Hemorrhage; Glutathione; Histamine Release; Indomethacin; Lipid Peroxides; Male; Mast Cells; Muramidase; Ofloxacin; Oxidative Stress; Rats; Rats, Wistar; Salmonella Infections, Animal; Sodium Chloride; Stomach Ulcer; Therapeutic Irrigation

The preventive effect of teprenone (6,10,14,18-teramethyl-5,9,13,17-nonadecatetaene-2-one), an anti-ulcer drug, on acute gastric mucosal lesion progression was examined in rats with a single intraperitoneal (i.p.) injection of compound 48/80 (0.75 mg/kg). Teprenone (20, 100 or 200 mg/kg), which was orally administered 0.5 h after compound 48/80 treatment at which time gastric mucosal lesions appeared, prevented gastric mucosal lesion development at 3 h after the treatment dose-dependently. Gastric mucosal tissues of compound 48/80-treated rats showed increases in myeloperoxidase (an index of neutrophil infiltration) and xanthine oxidase activities and thiobarbituric acid reactive substances (an index of lipid peroxidation) content and decreases in Se-glutathione peroxidase activity and hexosamine and vitamin E contents at 3 h after the treatment. Post-administered teprenone attenuated all these changes dose-dependently. These results indicate that teprenone prevents acute gastric mucosal lesion progression in compound 48/80-treated rats possibly by suppressing gastric mucus depletion, neutrophil infiltration and oxidative stress in the gastric mucosal tissue.

Topics: Animals; Anti-Ulcer Agents; Diterpenes; Gastric Mucosa; Glutathione Peroxidase; Hexosamines; Histamine; Male; p-Methoxy-N-methylphenethylamine; Peroxidase; Rats; Regional Blood Flow; Serotonin; Stomach Ulcer; Thiobarbituric Acid Reactive Substances; Vitamin E; Xanthine Oxidase

Infection of Salmonella typhimurium (Salmonella typhi) can lead to various organ diseases. This research first proposed that Salmonella typhi-infection could result in gastric oxidative stress and hemorrhagic ulcers that were ameliorated by ofloxacin, lysozyme chloride and several antioxidants, including exogenous glutathione (GSH), allopurinol and dimethylsulfoxide (DMSO). Male Wistar rats were given intrajejunally the live culture of Salmonella typhi [1 x 10(10) colony-forming unit (CFU)/rat] and followed by deprivation of food for 36 h. Age-matched control rats received vehicle only. Rat stomachs were irrigated for 3 h with either normal saline or a simulated gastric juice containing 100 mM HCl, 17.4 mM pepsin and 54 mM NaCl. Infection of Salmonella typhi produced an aggravation of ulcerogenic factors, including enhancing gastric acid back-diffusion, mucosal lipid peroxide generation and hemorrhagic ulcer as well as an attenuation of mucosal GSH level. Intragastric irrigation of gastric juice caused further aggravation of these gastric biochemical parameters. This exacerbation of ulcerogenic factors was abolished by pretreatment of ofloxacin and lysozyme chloride. Antioxidants, such as reduced GSH, allopurinol and DMSO also produced significant (P<0.05) amelioration of gastric damage in Salmonella typhi-infected rats. In conclusion, infection of Salmonella typhi substantially caused gastric oxidative stress and disruption of gastric mucosal barriers, consequently resulted in gastric hemorrhagic ulcerations that were effectively ameliorated by ofloxacin, lysozyme chloride and various antioxidants.

Topics: Allopurinol; Animals; Anti-Infective Agents; Dimethyl Sulfoxide; Free Radical Scavengers; Gastric Juice; Gastric Mucosa; Gastrointestinal Hemorrhage; Glutathione; Lipid Peroxides; Male; Muramidase; Ofloxacin; Oxidative Stress; Rats; Rats, Wistar; Salmonella Infections, Animal; Salmonella typhimurium; Sodium Chloride; Stomach Ulcer; Therapeutic Irrigation

Reactive oxygen species (ROS) are reportedly associated with gastric ulcer. We previously reported the use of an in vivo 300-MHz electron spin resonance (ESR) spectroscopy/nitroxyl probe technique to detect *OH generation in the stomachs of rats with gastric ulcers induced by NH4OH. However, this is an acute ulcer model, and the relationship between in vivo ROS generation and lesion formation remains to be clarified. To address this question, the same technique was applied to a sub-acute water immersion restraint (WIR) model. A nitroxyl probe that was less membrane-permeable was orally administered to WIR-treated rats, and the spectra in the gastric region were obtained by in vivo ESR spectroscopy. The signal intensity of the orally administered probe was clearly changed in the WIR group, but no change occurred in the control group. Both enhanced signal decay and neutrophil infiltration into mucosa were observed 2h after WIR with little formation of any mucosal lesions. The enhanced signal decay was caused by *OH generation, based on the finding that the decay was suppressed by mannitol, desferrioxamine and catalase. Intravenous treatment with either anti-neutrophil antibody or allopurinol also suppressed the enhanced signal decay, and allopurinol depressed neutrophil infiltration into the mucosa. In rats treated with WIR for 6 h, lesion formation was suppressed by 50% with all antioxidants used in this experiment except anti-neutrophil antibody. These findings suggest that *OH, which is generated in the stomach via the hypoxanthine/xanthine oxidase system upon neutrophil infiltrated into the mucosa, induces mucosal lesion formation, but that it accounts for only half the cause of lesion formation.

Topics: Allopurinol; Animals; Antioxidants; Cyclic N-Oxides; Electron Spin Resonance Spectroscopy; Gastric Mucosa; Hydroxyl Radical; Immersion; Magnetic Resonance Imaging; Male; Models, Animal; Neutrophil Infiltration; Peroxidase; Pyrrolidines; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Stomach Ulcer; Stress, Physiological

1. There are conflicting reports as to the protective effect of coadministered native superoxide dismutase (SOD) and catalase against gastric mucosal lesions in rats with water immersion restraint (WIR) stress. It is unclear how coadministered native SOD and catalase protect against WIR stress-induced gastric mucosal lesions. Therefore, in the present study, we re-examined the protective effect of coadministered native SOD and catalase against gastric mucosal lesions in rats with WIR stress. 2. Gastric mucosal lesions were induced in Wistar rats by 3 h WIR. Rats were injected subcutaneously with a mixture of purified bovine erythrocyte SOD and bovine liver catalase 1 h before the onset of WIR. Ulcer index, serum SOD, catalase and xanthine oxidase (XO), uric acid and gastric mucosal SOD, catalase, XO, myeloperoxidase (MPO; an index of tissue neutrophil infiltration), non-protein sulfhydryl (NP-SH) and thiobarbituric acid-reactive substances (TBARS; an index of lipid peroxidation) were assayed in all rats used. 3. Rats with 3 h WIR showed gastric mucosal lesions. Pre-administration of SOD plus catalase to rats with WIR prevented lesion formation. In the serum of rats with WIR alone, XO activity and uric acid concentration increased, whereas SOD and catalase activities did not change. Pre-administration of SOD plus catalase to rats with WIR did not affect increased serum XO activity and uric acid concentration, but did increase serum SOD and catalase activities. In the gastric mucosa of rats with WIR alone, increases in MPO activity and TBARS concentration and a decrease in NP-SH concentration occurred, whereas XO, SOD and catalase activities did not change. Pre-administration of SOD plus catalase to rats with WIR attenuated the changes in gastric mucosal MPO activity and TBARS and NP-SH concentrations, but did not affect gastric mucosal XO, SOD and catalase activities. Pre-administration of SOD plus catalase (in an inactivated form) to rats with WIR had no effect on gastric mucosal lesion formation and the levels of serum and gastric mucosal parameters studied. 4. These results indicate that coadministered native SOD and catalase protect against gastric mucosal lesions in rats with WIR stress and suggest that this protective effect of coadministered native SOD and catalase could be due to their activity to scavenge XO-derived active oxygen species that are increased in the blood.

Topics: Animals; Antioxidants; Catalase; Gastric Mucosa; Peroxidase; Rats; Rats, Wistar; Stomach Ulcer; Stress, Psychological; Sulfhydryl Compounds; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Uric Acid; Xanthine Oxidase

The protective effect of ebselen, which possesses glutathione peroxidase-like activity and antioxidative and anti-inflammatory properties, against the progression of acute gastric mucosal lesions was examined in rats with a single intraperitoneal injection of compound 48/80 (0.75 mg/kg). Ebselen (50, 100 or 200 mg/kg) was orally administered 0.5 h after compound 48/80 treatment, at which time gastric mucosal lesions appeared. Post-administered ebselen suppressed gastric mucosal lesion progression at 3 h after compound 48/80 treatment dose-dependently, although no dose of ebselen affected the decreased gastric mucosal blood flow and increased serum serotonin and histamine concentrations found at 3 h after the treatment. A decrease in Se-glutathione peroxidase activity and increases in myeloperoxidase and xanthine oxidase activities and the concentration of thiobarbituric acid reactive substances were found in gastric mucosal tissues at 0.5 h after compound 48/80 treatment, and these changes were further enhanced at 3 h. Post-administered ebselen attenuated all these changes found at 3 h after compound 48/80 treatment dose-dependently. The present results indicate that ebselen exerts a protective effect against the progression of compound 48/80-induced acute gastric mucosal lesions in rats, and they suggest that this protective effect of ebselen could be due to its glutathione peroxidase-like activity and its antioxidative and anti-inflammatory properties.

Topics: Acute Disease; Administration, Oral; Animals; Anti-Ulcer Agents; Azoles; Dose-Response Relationship, Drug; Gastric Mucosa; Histamine; Isoindoles; Male; Organoselenium Compounds; p-Methoxy-N-methylphenethylamine; Peroxidase; Rats; Rats, Wistar; Regional Blood Flow; Serotonin; Stomach Ulcer; Xanthine Oxidase

The preventive effect of ebselen, a seleno-organic compound, which is known to possess glutathione peroxidase-like activity and antioxidative and anti-inflammatory properties, on the development of acute gastric mucosal lesions was examined in rats with a single injection of compound 48/80 (0.75 mg/kg, i.p.), a mast cell degranulator. Pre-administration of ebselen (p.o.) at a dose of 50 or 100 mg/kg, but not 10 mg/kg, prevented gastric mucosal lesion development at 3 h, but not gastric mucosal lesion formation at 0.5 h, after compound 48/80 injection, although any dose of pre-administered ebselen did not affect decreased gastric mucosal blood flow and increased serum serotonin and histamine concentrations found at 0.5 and 3 h after compound 48/80 injection. A decrease in Se-glutathione peroxidase activity and increases in the activities of myeloperoxidase, an index of tissue neutrophil infiltration, and xanthine oxidase and the concentration of thiobarbituric acid reactive substances, an index of lipid peroxidation, were found in gastric mucosal tissues at 0.5 h after compound 48/80 injection and these changes were further enhanced at 3 h. Pre-administration of ebselen (p.o.) at a dose of 50 or 100 mg/kg, but not 10 mg/kg, attenuated all these changes found at 3 h after compound 48/80 injection. These preventive effects of ebselen occurred in a dose-dependent manner. The present results indicate that pre-administered ebselen prevents the development of compound 48/80-induced acute gastric mucosal lesions in rats, and suggest that this preventive effect of ebselen could be due to its glutathione peroxidase-like activity and antioxidative and anti-inflammatory properties.

Topics: Animals; Anti-Ulcer Agents; Azoles; Gastric Mucosa; Glutathione Peroxidase; Histamine; Isoindoles; Lipid Peroxidation; Male; Organoselenium Compounds; p-Methoxy-N-methylphenethylamine; Rats; Rats, Wistar; Serotonin; Stomach Ulcer; Thiobarbituric Acid Reactive Substances; Xanthine Oxidase

Ischemia followed by reperfusion (I/R) induces gastric lesions, probably due to excessive formation of free radicals, but the role of the scavenger of these radicals, proinflammatory cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), in the healing of these lesions has not been extensively studied. It is also unknown whether expression of intercellular adhesion molecule-1 (ICAM-1), which mediates neutrophil-induced injury and neutrophil infiltration, is involved in the recovery from I/R lesions.. I/R lesions were induced in Wistar rats by applying a small clamp to the celiac artery for 30 min (ischemia phase), followed by the removal of the clamp for 60 min (reperfusion phase). The influence of I/R on gastric secretion was also tested in rats equipped with a gastric fistula (GF) without or with the exposure to a standard period of I/R. Two series of rats (A and B) were used to determine the effects of exogenous and endogenous superoxide dismutase SOD (series A) and allopurinol, a xanthine oxidase inhibitor (series B), on the mucosal recovery from the gastric lesions induced by I/R. The animals were killed immediately after the exposure to I/R (0 h) and at 3 h, 24 h, or 3, 5, or 10 days after this I/R, the area of gastric lesions being measured by planimetry, and the gastric blood flow (GBF) determined by the H2 gas clearance method. Blood was withdrawn for measurement of plasma IL-1beta and TNF-alpha levels with enzyme-linked immunosorbent assay, and plasma gastrin with radioimmunoassay. Biopsy samples of oxyntic mucosa were taken for the assessment of SOD, IL-1beta, TNF-alpha, and ICAM-1 mRNAs by reverse-transcription polymerase chain reaction and Southern blot.. Exposure to I/R resulted in acute gastric erosions, with the maximal increase of the area of these lesions observed 3 h after the end of I/R. This effect was accompanied by a decrease in the GBF, a significant increase in blood free radicals and plasma gastrin increments, and almost complete suppression of gastric secretion. Starting 24 h after I/R, the gastric superficial lesions progressed into deeper ulcers that healed progressively within 10 days, and this was accompanied by gradual restoration of the gastric secretion and the GBF. Treatment with SOD and allopurinol accelerated significantly the healing of I/R erosions, and this effect was accompanied by a significant increase in the GBF and the attenuation of blood free radicals. At 0, 3, and 12 h after I/R a significant decrease in SOD mRNA was observed, whereas expression of TNF-alpha, IL-1beta, and ICAM-1 showed a progressive increase starting immediately after I/R, reaching a maximum on day 3. The plasma level of TNF-alpha and IL-1beta started to increase on day 3 and peaked on day 5 after I/R, being still significantly higher at day 10 than that measured in the vehicle-treated control gastric mucosa. On day 10 the gastric ulcers were almost completely healed, and a decrease in the expression for TNF-alpha, IL-1beta, and ICAM-1 mRNA and an increase in the expression of SOD mRNA were observed.. 1) exposure to I/R produces gastric lesions mediated by the excessive formation of free radicals, resulting in suppression of both gastric microcirculation and secretory activity of the stomach; 2) SOD and allopurinol accelerate the healing of I/R lesions, probably due to suppression of oxygen free radicals and improvement of gastric microcirculation; and 3) the upregulation of SOD mRNA, with subsequent increase in the SOD production and local release of IL-1beta and TNF-alpha, may activate ICAM-1 expression and neutrophil infiltration, which appear to play an important role in the progression of I/R-induced acute gastric erosions into chronic ulcers.

Topics: Allopurinol; Animals; Cytokines; Free Radical Scavengers; Free Radicals; Gastric Juice; Gastric Mucosa; Gene Expression Regulation; Intercellular Adhesion Molecule-1; Interleukin-1; Male; Rats; Rats, Wistar; Reperfusion Injury; Stomach Ulcer; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Garcinol, a polyisoprenylated benzophenone derivative, was purified from Garcinia indica fruit rind, and its free radical scavenging activity was studied using electron spin resonance (ESR) spectrometry. In the hypoxanthine/xanthine oxidase system, emulsified garcinol suppressed superoxide anion to almost the same extent as DL-alpha-tocopherol by weight. In the Fenton reaction system, garcinol also suppressed hydroxyl radical more strongly than DL-alpha-tocopherol. In the H(2)O(2)/NaOH/DMSO system, garcinol suppressed superoxide anion, hydroxyl radical, and methyl radical. It was thus confirmed that this derivative is a potent free radical scavenger and able to scavenge both hydrophilic and hydrophobic ones including reactive oxygen species. Orally administered garcinol prevented acute ulceration in rats induced by indomethacin and water immersion stress caused by radical formation. These results suggested garcinol might have potential as a free radical scavenger and clinical application as an antiulcer drug.

Topics: Animals; Anti-Ulcer Agents; Electron Spin Resonance Spectroscopy; Free Radical Scavengers; Fruit; Indomethacin; Male; Plants, Medicinal; Rats; Rats, Wistar; Stomach Ulcer; Stress, Psychological; Terpenes; Vitamin E; Xanthine Oxidase

The preventive effect of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract (TJ-15), a traditional Chinese herbal medicine for the therapies of gastric ulcers and gastritis, on the development of stress-induced acute gastric mucosal lesions was examined in rats with water immersion restraint (WIR) stress. Simultaneous p.o. administration of TJ-15 at a dose of 20, 100 or 250 mg/kg prevented dose-dependently gastric mucosal lesion development in rats subjected to WIR stress over a 6-h period. In the gastric mucosa of rats with WIR stress alone, lipid peroxide concentration and xanthine oxidase (XOD) and myeloperoxidase--an index of neutrophil infiltration--activities increased with lesion development, while nonprotein SH concentration decreased. The simultaneous administration of TJ-15 attenuated all these changes with gastric mucosal lesion development in a dose-dependent manner. These results indicate that simultaneously administered TJ-15 exerts a preventive effect on the development of WIR stress-induced acute gastric lesions in rats, and suggest that the preventive effect of TJ-15 could be due to its preventive actions on enhanced sulfhydryl oxidation and lipid peroxidation via oxygen free radicals generated by the xanthine-xanthine oxidase system and infiltrated neutrophils in the gastric mucosa and on neutrophil infiltration into the tissue.

Topics: Animals; Drugs, Chinese Herbal; Gastric Mucosa; Lipid Peroxidation; Male; Peroxidase; Rats; Rats, Wistar; Stomach Ulcer; Stress, Physiological; Xanthine Oxidase

Cigarette smoking is associated with peptic ulceration in humans. A mechanistic study of the potentiating effects of cigarette smoking on acetic acid-induced gastric ulceration in rats was hence performed. Rats were exposed to 0, 2 or 4% of cigarette smoke for three 1-hr periods during the 24 hr starvation before ulcer induction. Cigarette smoke exposure potentiated ulcer formation which was accompanied by a reduction of gastric blood flow at the ulcer base and ulcer margin. Further studies showed that cigarette smoke exposure alone did not cause any macroscopic injury in the stomach but significantly decreased the basal gastric blood flow in a concentration-dependent manner, which was coupled with an increase in mucosal xanthine oxidase (XO) activity. Pretreatment with allopurinol (Allo, 5 mg/kg, i.v.), a XO inhibitor, partially prevented the potentiating effect of cigarette smoke exposure on ulcer formation and also significantly improved the gastric blood flow. Ulcer induction itself dramatically increased constitutive nitric oxide synthase (cNOS) activity and prostaglandin E2 (PGE2) level in the gastric mucosa. However, the increment of cNOS activity but not PGE2 level was markedly attenuated by cigarette smoke exposure. Sodium nitroprusside (SNP, 25 or 50 microg/kg, i.v.), a nitric oxide (NO) donor, completely abolished the potentiating effect of cigarette smoke exposure on ulcer formation and also reversed the adverse effect on gastric blood flow. Thus, XO activation and cNOS reduction in the gastric mucosa are closely associated with the potentiating action of cigarette smoke exposure on ulcer formation in rats.

Topics: Acetic Acid; Allopurinol; Animals; Dinoprostone; Enzyme Activation; Gastric Mucosa; Male; Nicotiana; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Nitroprusside; Plants, Toxic; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Smoke; Stomach Ulcer; Xanthine Oxidase

The antiulcer activity of cacao liquor water-soluble crude polyphenols (CWSP) was examined. CWSP, alpha-tocopherol, sucralfate (500 mg/kg), and cimetidine (250 mg/kg) were orally administered to male SD rats 30 minutes before ethanol treatment. 5 ml/kg of ethanol given intragastrically caused lesions in mucosa of the glandular stomach. CWSP caused a reduction of such hemorrhagic lesions as well as cimetidine and sucralfate which are typical antiulcer drugs, but alpha-tocopherol was less effective. Thiobarbituric acid reactive substances in gastric mucosa significantly increased with ethanol administration. CWSP treatment significantly reduced this change. The administration of ethanol extensively increased myeloperoxidase (MPO) but not xanthine oxidase (XOD) activity. CWSP reduced the activities of both enzymes; they were considered the main sources of oxygen radicals. According to an in vitro study, CWSP directly reducted XOD but not MPO. These results suggest that the antiulcer mechanism of CWSP was not only radical scavenging but also modulation of leukocyte function.

Topics: Animals; Anti-Ulcer Agents; Antioxidants; Cacao; Chromatography, High Pressure Liquid; Cimetidine; Dose-Response Relationship, Drug; Ethanol; Flavonoids; Gastric Mucosa; Lipid Peroxidation; Male; Peroxidase; Phenols; Polymers; Polyphenols; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Sucralfate; Thiobarbituric Acid Reactive Substances; Uric Acid; Vitamin E; Xanthine Oxidase

Sprague-Dawley rats were restrained at 4 degrees C for 2 h (stress). Tungstic acid in a single dose of 0.01, 0.1, 1, 10, 100 or 300 mg/kg (dissolved in distilled water) was administered intragastrically to animals 30 min prior to stress. Stress induced significant gastric mucosal damage, whereas tungstic acid pretreatment dose-dependently reduced lesion formation. Doses of tungstic acid of 1 mg/kg and higher significantly (P < 0.05-0.001) decreased ulcers. The mucosal mast cell counts in rats pretreated with tungstic acid were significantly higher than those of control rats. In motility experiments using oral administration of amberlite pellets, pretreatment with tungstic acid dose-dependently reduced the gastric emptying rate during a 1 h period of stress. Gastric mucosal xanthine oxidase and superoxide dismutase (SOD) activities, after pretreatment with a single dose of tungstic acid, were not altered in stressed animals. It is suggested that tungstic acid effectively antagonizes stress-induced gastric ulcers, possibly by decreasing motility and mass cell degranulation. Xanthine oxidase and SOD activities and mucous content were not changed in the gastric mucosa by the present method of tungstic acid administration.

Topics: Animals; Cell Degranulation; Cold Temperature; Dose-Response Relationship, Drug; Female; Gastric Emptying; Gastric Mucosa; Mast Cells; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Stress, Physiological; Superoxide Dismutase; Tungsten Compounds; Xanthine Oxidase

We have revealed that acute gastric mucosal injury induced by a single ischemia-reperfusion (I-R) treatment develops into an ulcerative lesion within a few days. In the present studies, we examined the effects of oral administration of sucralfate on gastric damage induced by I-R. Sucralfate (1-100 mg/kg, 15 min before I-R) significantly reduced the total erosion area observed immediately after I-R. A high dose of sucralfate (30-100 mg/kg) inhibited the increase in the thiobarbituric acid-reactive substances, an index of lipid peroxidation, induced by I-R, although a low dose of it failed. When sucralfate (30 mg/kg, once a day) was orally administered after I-R, it prevented mucosal damage from developing into gastric ulcers: the total area of the ulcers was significantly reduced compared to that without sucralfate administration 72 h after I-R. High concentrations of sucralfate (3-10 mg/ml) reduced the superoxide radicals generated by leukocytes or xanthine-xanthine oxidase, and protected erythrocyte membrane ghosts against lipid peroxidation induced by hydrogen peroxide and Fe2+ in vitro. These results indicate that sucralfate may prohibit both the generation of acute gastric mucosal injury and its progression to ulcer induced by I-R, probably due to a cytoprotective action on the mucosal surface. However, the protective mechanism may involve an inhibitory action on superoxide and hydroxyl radicals at high doses.

Topics: Animals; Anti-Ulcer Agents; Erythrocyte Membrane; Gastric Mucosa; Hydroxyl Radical; Leukocytes; Lipid Peroxides; Male; Rats; Rats, Wistar; Reactive Oxygen Species; Reperfusion Injury; Stomach Ulcer; Sucralfate; Superoxides; Thiobarbituric Acid Reactive Substances; Xanthine Oxidase

Plaunatol, an anti-ulcer drug, increases prostaglandin content in gastric tissue but its effect on radical-mediated gastric damage or activity against reactive oxygen species is unknown. We examined the effects of oral administration of plaunotol (Kelnac) on the acute gastric mucosal lesion and its progression to ulcer lesion induced by ischaemia-reperfusion in rats. Plaunotol (30 and 100 mg kg-1, 15 min before ischaemia) significantly reduced the total erosion area observed immediately after ischaemia-reperfusion. When plaunotol (30 and 100 mg kg-1, once a day) was administrated orally 60 min after reperfusion, it prevented the progression from erosion to ulcer. At 72 h after ischaemia-reperfusion, the total area of ulcers lesions was significantly reduced compared with that without plaunotol administration. Furthermore, treatment with plaunotol (100 mg kg-1) significantly increased prostaglandin E2 content in gastric tissues of both acute gastric mucosal lesion and gastric ulcer lesion. In in-vitro experiments, plaunotol (1-3 mg mL-1) reduced the superoxide radicals generated by leucocytes, but not by xanthine oxidase. These results indicate that plaunotol has protective effects on both the onset of acute gastric mucosal injury and its progression to ulcer lesion induced by ischaemia-reperfusion. Both effects of plaunotol on increase in prostaglandin content in gastric tissues and inhibition of superoxide radical from leucocytes may play important roles on the protection against gastric mucosal injury.

Topics: Animals; Anti-Ulcer Agents; Dinoprostone; Diterpenes; Fatty Alcohols; Gastric Mucosa; Humans; In Vitro Techniques; Leukocytes; Male; Rats; Rats, Wistar; Reperfusion Injury; Stomach Ulcer; Superoxides; Xanthine Oxidase

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.

Topics: Allopurinol; alpha-Amylases; Analysis of Variance; Animals; Disease Models, Animal; Enzyme Inhibitors; Gastric Mucosa; Immersion; Lipid Peroxidation; Male; Neutrophil Activation; Neutrophils; Peroxidase; Plant Proteins; Rats; Rats, Wistar; Reference Values; Stomach Ulcer; Stress, Physiological; Trypsin Inhibitors; Wound Healing; Xanthine Oxidase

This study examined the role of oxygen-derived free radicals, the potential involvement of neutrophils and the possible mucosal vascular permeability changes involved in the pathogenesis and evolution of gastric mucosal lesions induced by acetic acid in the rat. Myeloperoxidase activity was assayed and used as an index of leukocyte infiltration. Application of acetic acid produced a significant increase in this activity 7 and 14 days after induction of chronic injury. Administration of hydroxyurea intraperitoneally was associated with a decrease in the severity of chronic ulceration and neutrophil infiltration into the gastric lesion. This effect was detectable enzymatically and microscopically. Orally administered allopurinol did not produce any beneficial effects on either the macroscopic and histological appearance or on vascular permeability. These results suggest that oxygen-derived free radicals may contribute to the formation and development of chronic lesions and that oxygen-derived free radicals were generated from neutrophils, but not from the xanthine oxidase pathway. These inflammatory cells may, therefore, have a lesive role in the origin and course of acetic acid ulcer disease.

Topics: Acetic Acid; Allopurinol; Animals; Antimetabolites; Capillary Permeability; Enzyme Inhibitors; Epithelium; Female; Hydroxyurea; Male; Neutrophils; Peroxidase; Rats; Rats, Wistar; Reactive Oxygen Species; Stomach Ulcer

Rebamipide, a novel antipeptic ulcer drug, 2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinone-4-yl]-propionic acid, was studied for its inhibitory effect on gastric xanthine oxidase activity and type conversion of the enzyme that has a profound role in free radical generation. Intraperitoneal administration of rebamipide at 60 mg/kg body weight reduced gastric mucosal hemorrhagic lesions and lipid peroxidation, which was proportional to the inhibitory effect of rebamipide on alcohol-induced xanthine oxidase-type conversion and enzyme activity. It was also observed that the activity of xanthine oxidase was significantly inhibited by administration of rebamipide at 60 mg/kg body weight, leading to a significant reduction of lipid peroxide content in alcohol-treated rats. The results suggest that alcohol-induced gastric mucosal lesions might be, in part, due to the increased activity of xanthine oxidase and type conversion rate of the enzyme and the protective effect of rebamipide on gastric mucosal lesions would result from its ability to protect against oxidative stress on gastric mucosal lesions of alcohol-treated rats.

Topics: Alanine; Animals; Anti-Ulcer Agents; Enzyme Inhibitors; Ethanol; Free Radicals; Lipid Peroxidation; Male; Peptic Ulcer Hemorrhage; Quinolones; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Stomach Ulcer; Xanthine Oxidase

Effects of treatment with free radical scavengers in the healing process of acetic acid-induced gastric ulcer on the ulcer aggravation induced by indomethacin were investigated. Gastric ulcers were produced on the anterior wall of the stomach of male Sprague-Dawley rats by submucosal injection of 20% acetic acid. To investigate the role of oxygen radicals, rats with gastric ulcer were treated with scavengers for six weeks and then treated with indomethacin (1 mg/kg/day). While superoxide dismutase (10,000 units/kg/day) did not affect the ulcer area after indomethacin treatment, allopurinol (50 mg/kg/day) slightly inhibited the increase in ulcer area. Dimethyl sulfoxide (1% solution, ad libitum) produced a significant decrease in size of the ulcer after indomethacin treatment. Increased lipid peroxides in the gastric mucosa after indomethacin treatment decreased significantly in the rats of the dimethyl sulfoxide and allopurinol groups. These results indicate that lipid peroxidation mediated by oxygen radicals plays an important role in the mechanism of ulcer aggravation induced by indomethacin.

Topics: Acetates; Acetic Acid; Allopurinol; Animals; Cyclooxygenase Inhibitors; Dimethyl Sulfoxide; Free Radical Scavengers; Free Radicals; Indomethacin; Lipid Peroxides; Male; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Stomach Ulcer; Superoxide Dismutase

Oxygen-derived radicals are implicated in the pathogenesis of tissue damage and ulcerogenesis. This study aimed to examine the effect of manganese, glycine, and carotene, oxygen radical scavengers, on ethanol-induced gastric lesions in the rat and on ethanol cytotoxicity in epithelial cell culture.. MnCl2 + glycine (12.5-50 mg/rat) were injected subcutaneously up to 6 h before oral administration of 1 ml of 96% ethanol, and 0.5 ml carrot juice or beta-carotene was given orally 30 min before the ethanol. Mucosal injury was evaluated 1 h later by gross and microscopic scoring. The effect of Mn2+ and carrot juice was also tested in monolayers of radiolabeled epithelial cells exposed to H2O2 + ethanol injury as expressed by the extent of the isotope leakage.. Mn2+ and glycine pretreatment dose-dependently reduced ethanol-induced gastric lesion formation. Protection was maximal when treatment was applied 4 h before the insult. Gross damage was also markedly prevented by pretreatment with carotenes and dimethylthiourea (DMTU, 75 mg/kg intraperitoneally) but not by allopurinol. Mixtures of subtoxic concentrations of ethanol and H2O2 were highly lethal for epithelial cell monolayers. In this model, cell death was markedly attenuated by catalase, DMTU, Mn2+, and carrot juice.. Ethanol-induced gastric mucosal damage may involve generation of oxygen-derived radicals, independent of the xanthine oxidase system. By acting as oxygen radical scavengers, Mn2+, glycine, and carotenes, like catalase and DMTU, provide significant gastroprotection.

Topics: Allopurinol; Animals; Antioxidants; Carotenoids; Cells, Cultured; Chlorocebus aethiops; Enzyme Inhibitors; Epithelium; Ethanol; Free Radical Scavengers; Gastric Mucosa; Glycine; Male; Manganese; Rats; Rats, Inbred Strains; Stomach Ulcer; Thiourea

We examined the effects of FK506, an immunosuppressive agent, on the genesis of water immersion stress-induced gastric lesions in rats. Using high-performance liquid chromatography, four kinds of prostaglandins, ie, 6-keto-prostaglandin F1 alpha, prostaglandin F2 alpha, prostaglandin E2, and prostaglandin D2, were detected, and no leukotrienes were detected in gastric mucosa in rats without stress. After 6 hr of stress, gastric lesions developed with decreases in all prostaglandin contents, and the emergence of peptide leukotrienes was observed. Intramuscular administration of FK506 (0.1, 0.25, 0.5, 1.0, and 2.0 mg/kg) reduced lesion index dose-dependently. Administration of FK506 at doses over 0.25 mg/kg decreased all prostaglandin contents, but did not affect the increase in leukotriene contents. Pretreatment with famotidine or omeprazole reduced lesion index, and the protective effects were equivalent to those of 1.0 mg/kg of FK506, although FK506 did not affect gastric secretion during water-immersion stress. Water-immersion stress did not change the activities of xanthine oxidase in either stomach or serum. Polyoxyethylene-modified superoxide dismutase did not prevent gastric lesions. Water-immersion stress significantly increased myeloperoxidase activity in gastric mucosa, and FK506 reduced the increase in myeloperoxidase activity induced by stress. From our results, other factors besides gastric acid secretion and tissue eicosanoid contents, such as chemoattractant factor, might also be involved in the genesis of water-immersion stress-induced gastric lesions in rats.

Topics: Animals; Famotidine; Gastric Mucosa; Immersion; Leukotrienes; Male; Omeprazole; Peroxidase; Polyethylene Glycols; Prostaglandins; Rats; Rats, Wistar; Stomach Ulcer; Stress, Physiological; Superoxide Dismutase; Tacrolimus; Xanthine Oxidase

This study was conducted to determine the beneficial effects of treating digestive disorders of (6E,12E)-tetradecadiene-8,10-diyne-1,3-diol diacetate (TDEYA) detected in the plasma in hydrolyzed form: (6E,12E)-tetradecadiene-8,10-diyne-1,3-diol (TDEY), following the oral administration of a decoction of Atractylodes rhizome to rats. Assessment was also made of the efficacy of TDEYA in experimental gastric disorder models. Oral administration of TDEYA at doses of 300 to 500 mg/kg suppressed the formation of gastric lesions induced by indometacin in a dose-dependent manner. TDEYA at a dose of 200 mg/kg suppressed gastric lesions induced by an ischemia-reperfusion injury model. TDEYA at doses of 100 to 300 mg/kg did not show suppressive effects on water immersion stress-induced gastric lesions. TDEYA showed no active oxygen species scavenging action, nor did it have any effect on superoxide dismutase activity in the stomach tissue. TDEYA at doses of 200 to 500 mg/kg significantly suppressed xanthine oxidase (XO) activity in the stomach tissue following its oral administration. The suppressive effects of TDEYA on lesion formation induced by indometacin and ischemia-reperfusion injury models would thus appear to be due in part to the inhibition of XO activity in the stomach tissue.

Topics: Acetylene; Administration, Oral; Alkynes; Animals; Anti-Ulcer Agents; Disease Models, Animal; Diynes; Dose-Response Relationship, Drug; Fatty Alcohols; Free Radical Scavengers; Gastric Mucosa; Indomethacin; Male; Plant Extracts; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reperfusion Injury; Stomach Ulcer; Superoxide Dismutase; Xanthine Oxidase

Adenosine deaminase (ADA), 5'-Nucleotidase (5NT), Xanthine oxidase (XO), Cu-Zn Superoxide dismutase (SOD) and Catalase (CAT) activities were determined in gastric juices from patients with gastric cancer, ulcer, gastritis and from healthy subjects. Enzyme activities were given as units per ml gastric juice and units per mg protein in gastric juice. ADA, 5NT and XO activities were found lower and protein concentrations were found higher in the cancer group than controls. There was however no significant difference between Cu-Zn SOD activities of the cancer and control groups. In all groups including control one, we could not find catalase activities in most of the samples. On the other hand, ADA, 5NT activities and protein concentrations in the gastric juice were lower in the gastritis group than control group. In the ulcer group, we found higher Cu-Zn SOD and XO activities and lower 5NT activity and protein concentrations compared with control values. In an attempt to establish statistical correlations between mean enzyme activities, pH and protein concentrations in the gastric juices of the groups, we found noticeable intra and inter-correlations, which indicated possible relations between DNA and free radical metabolizing enzymes.

Topics: 5'-Nucleotidase; Adenosine Deaminase; Adult; Aged; Catalase; Female; Free Radicals; Gastric Juice; Gastritis, Atrophic; Humans; Male; Middle Aged; Stomach Neoplasms; Stomach Ulcer; Xanthine Oxidase

This study examined the role of oxygen-derived free radicals in the pathogenesis of gastric mucosal lesions induced by HCl/ethanol. Superoxide dismutase, and catalase, and their combination reduced gastric lesion formation in mice. Gastric lesions were also reduced in mice treated with cyclophosphamide or anti-neutrophils, but not in mice treated with allopurinol or desulphated-carrageenan. Cobra venom factor did not reduce lesion formation. These results suggested that oxygen-free radicals may contribute to the formation of gastric mucosal lesions induced by HCl/ethanol, and that oxygen radicals were generated from neutrophils but not from xanthine oxidase. Anti-ulcer pectic polysaccharide, bupleuran 2IIc, which was recently isolated from the roots of Bupleurum falcatum L., showed potent inhibition of HCl/ethanol-induced gastric lesions in mice. Bupleuran 2IIc seemed to scavenge hydroxyl radical effectively. It was suggested that this anti-ulcer polysaccharide may provide protection to the gastric mucosa by scavenging oxygen-free radicals.

Topics: Allopurinol; Animals; Anti-Ulcer Agents; Carrageenan; Cattle; Cyclophosphamide; Ethanol; Free Radical Scavengers; Gastric Mucosa; Hydrochloric Acid; Hydroxides; Hydroxyl Radical; Male; Mice; Mice, Inbred ICR; Neutrophils; Pectins; Rabbits; Reactive Oxygen Species; Stomach Ulcer; Superoxides

Topics: Animals; Free Radicals; Gastric Mucosa; Malondialdehyde; Rats; Somatostatin; Stomach Ulcer; Stress, Physiological; Xanthine Oxidase

In the present work, the role of oxygen-derived free radicals in the pathogenesis of the gastric mucosal injury induced by cold-restraint stress was studied in rats. The results were as follows. (1) In rats pretreated with superoxide dismutase (SOD), a scavenger of superoxide anions, or with dimethyl sulfoxide and mannitol, scavengers of hydroxyl radicals, the gastric lesions induced by stress became much less extensive. (2) The mucosal content of malondialdehyde, a metabolic product of lipid peroxides, was significantly increased during stress. (3) Histochemical study revealed that the gastric mucosa abounded in xanthine oxidase (XO), the enzymic activity of which was increased during stress. In the rats pretreated with allopurinol, to inhibit XO activity, the extent of gastric mucosal lesions was decreased significantly. These suggested that oxygen free radicals might be one of the important factors in inducing gastric mucosal injury during stress and the increase of XO activity might be responsible for the production of the radicals.

Topics: Animals; Free Radical Scavengers; Free Radicals; Gastric Mucosa; Male; Oxygen; Rats; Rats, Wistar; Stomach Ulcer; Stress, Physiological; Xanthine Oxidase

Chronic nicotine treatment worsens stomach mucosal damage by cold (4 degrees C) and restraint (stress): it dose- and time-dependently intensifies stress-evoked gastric glandular ulceration, mast cell degranulation and motility. Nicotine 50 micrograms/ml drinking water, given ad libitum to female Sprague-Dawley rats for 10 days, increases the sensitivity of the isolated stomach strip to acetylcholine-induced contractions; atropine abolishes this action. The isolated anococcygeus muscle from nicotine-treated male rats shows increased sensitivity to noradrenaline-induced contractions, but not to those by acetylcholine. Hexamethonium or atropine pretreatment antagonises stress-induced gastric effects in nicotine-drinking rats. Muscarinic M1- and M2-, but not M3-, receptor block (by pirenzepine, AF-DX 116BS and HHSiD, respectively) inhibits stress ulcer formation in female rats. Although tobacco smoking has been reported to increase free radical formation, mucosal xanthine oxidase which initiates free radical formation is uninfluenced by nicotine; antagonising this enzyme (by allopurinol) or hydroxyl free radical scavenging (by dimethylsulfoxide) does not lessen the effect of nicotine on stress-evoked ulceration. The findings suggest that chronic nicotine treatment produces partial ganglionic blockade of the vagal nerve which leads to muscarinic receptor supersensitivity. This phenomenon contributes significantly to the ulcer-worsening mechanism; muscarinic M1- and M2-receptors appear to be involved. The gastric ulcer-aggravating effect of nicotine in stressed rats appears not to be due to increased free radical formation.

Topics: Animals; Female; Free Radicals; Gastric Mucosa; Male; Nicotine; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic; Stomach Ulcer; Stress, Physiological; Xanthine Oxidase

In this study we examined the role of oxygen-derived free radicals in the pathogenesis of acute gastric mucosal lesion induced by obstructive jaundice in rats. Rats were divided into 4 groups as follows: control (sham operation), jaundiced (ligation and dissection of bile duct), vagotomized (truncal vagotomy), and vagotomized with jaundice group. The water immersion restraint procedure was performed. The water immersion restraint procedure was performed. The results obtained are as follows: jaundiced group showed significant increase of ulcer index (UI) and significant decrease of gastric mucosal blood flow (GMBF) and gastric mucosal potential difference (PD). However, intragastric pH (pH) was unchanged compared to the control group. Oxygen radical generating system (gastric mucosal XOD activity and thiobarbiturate acid) and oxygen radical scavenging system (gastric mucosal SOD activity and GSH-px activity) were higher than those of control group. Vagotomized group showed significant increase of pH compared to the control group. Oxygen generating system and scavenging system were unchanged compared to the control group. Vagotomized with jaundice group showed depression of UI and improvement of oxygen radical generating system and scavenging system. However GMBF, PD nad pH were unchanged compared to the jaundiced group. These results suggest that oxygen radical play some role in the development of acute gastric mucosal lesion induced by obstructive jaundice.

Topics: Animals; Cholestasis; Free Radicals; Gastric Mucosa; Hydrogen-Ion Concentration; Lipid Peroxides; Male; Rats; Rats, Wistar; Reactive Oxygen Species; Regional Blood Flow; Stomach Ulcer; Stress, Physiological; Superoxide Dismutase; Xanthine Oxidase

The influence of stress on the structure of the gastric mucosal capillary network was investigated in an experimental model using scanning electron microscopy (SEM) to study corrosion casts of the gastric microvasculature. An index of microcirculatory patency was devised to improve the objectivity of SEM. Stress (mean score 42.4 +/- 4.7) severely disrupted the structure of the mucosal capillary network when compared with controls (mean 5.0 +/- 2.9) (P < 0.01). Disruption of the microvascular network was significantly reduced by pretreatment with allopurinol, cimetidine, and misoprostol, these groups having mean damage scores of 17.4 +/- 5.8, 21.2 +/- 7.9, and 28.6 +/- 9.3, respectively, when compared with untreated stressed controls in which the mean score was 42.4 +/- 4.7 (P < 0.02). Microvascular disruption is a significant factor in stress ulceration and the efficacy of allopurinol in minimizing the stress-induced disruption of the microvascular network provides further indirect evidence for the role of ischemia and oxygen-derived free radical generation in its etiology.

Topics: Allopurinol; Animals; Capillaries; Cimetidine; Female; Gastric Mucosa; Microcirculation; Microscopy, Electron, Scanning; Misoprostol; Rats; Rats, Wistar; Restraint, Physical; Stomach Ulcer; Stress, Physiological; Vascular Patency

Acute gastric stress ulceration occurs frequently in severely ill patients. Mucosal ischemia is central to the etiology of stress ulceration. The ability of the mucosa to restore continuity when damaged is one of the most important of the local defence mechanisms against injury. The aims of this study were to investigate this restitutive process during stress ulcer formation and to determine the effect of prophylaxis against stress ulceration on gastric mucosal cell kinetics. Nuclear DNA was radiolabeled in vivo with tritiated thymidine, and after autoradiography the position and number of labeled cells along the gastric mucosal gland were determined. Wistar rats were studied immediately and 48 hr after cold restraint stress. The labeling index in the proliferative zone of the gastric mucosa was significantly suppressed immediately after stress (12.58% vs 16.81% for unstressed controls, P < 0.001). This effect persisted for 48 hr after stress (9.89% vs 16.35% for unstressed controls, P < 0.001). Prophylaxis against stress ulceration with cimetidine or allopurinol prevented this suppression of gastric mucosal cell kinetics and promoted early migration of labeled cells towards the surface of the mucosal gland. Allopurinol prophylaxis was associated with migration of mucosal cells immediately following stress greater than that following cimetidine prophylaxis (14.0% vs 9.3% surface layer labeling index, P < 0.01). Allopurinol, a xanthine oxidase inhibitor, reduces oxygen free radical production during ischemia reperfusion injury. These results emphasise the importance of the gastric mucosal defence mechanisms in protection against injury and indicate the role of ischemia in the aetiology of acute gastric stress ulceration.

Topics: Allopurinol; Animals; Cell Division; Cell Movement; Cimetidine; DNA; Gastric Mucosa; Kinetics; Male; Rats; Rats, Wistar; Restraint, Physical; Stomach Ulcer; Stress, Physiological

The role of sucralphate in prevention of acute gastric injuries and its comparison with free radical blockers such as allopurinol, soybean trypsin inhibitor and superoxidase dismutase in the ischemia-reperfusion model by total occlusion of the coeliac artery in Wistar rats, was studied. The gross gastric mucosal necrotic area was 80%. In contrast with the antioxidant drugs the necrotic area attained was between 7 to 15%, while with sucralphate, an antioxidant-cytoprotective drug that enhances the gastric defensive barrier, the prevention of the secondary aggression induced by free radicals was more important.

Topics: Acute Disease; Allopurinol; Animals; Female; Gastric Mucosa; Rats; Rats, Wistar; Reperfusion Injury; Stomach; Stomach Ulcer; Sucralfate; Superoxide Dismutase; Trypsin Inhibitor, Kunitz Soybean

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

Refractory peptic ulceration refers to those gastric and duodenal ulcers that are slow to heal despite active treatment. Oxygen-derived free radicals are cytotoxic and promote tissue injury. This report shows that radical scavengers stimulate the healing of refractory peptic ulceration, thus, providing a valuable method for the treatment of such ulceration.

Topics: Adult; Allopurinol; Chronic Disease; Cimetidine; Dimethyl Sulfoxide; Duodenal Ulcer; Female; Free Radical Scavengers; Free Radicals; Humans; Hydroxides; Hydroxyl Radical; Male; Middle Aged; Stomach Ulcer

The role of oxygen-derived free radicals in the pathogenesis of acute gastric ulceration induced by indomethacin (Indo) was investigated in rats. Gastric damage was assessed by blood-to-lumen leakage of 51Cr-EDTA, as well as by measuring the extent of macroscopically visible hemorrhagic lesions. The stomach was perfused with isotonic saline for 30 min, followed by Indo (10 mg/ml for 30 min) and HCl (100 mM for 60 min). Rats were given a continuous intravenous infusion of the antioxidant enzymes superoxide dismutase (SOD) or catalase or the iron-chelating agent deferoxamine. Additional rats received an intravenous infusion of the vehicle (control group) or were pretreated with prostaglandin E2 (100 micrograms/kg ip) or allopurinol (50 mg/kg po). Exposure of the stomach to Indo caused a fourfold increase in 51Cr-EDTA leakage compared with that observed in rats receiving only the vehicle for Indo. Subsequent exposure of the stomach to HCl resulted in a further twofold increase in 51Cr-EDTA leakage. Treatment with SOD, catalase, or deferoxamine significantly (P less than 0.05) reduced 51Cr-EDTA leakage during the intragastric perfusion with Indo and during the subsequent exposure to HCl. Pretreatment with PGE2 reduced 51Cr-EDTA leakage during perfusion with HCl only. Pretreatment with allopurinol did not significantly affect 51Cr-EDTA leakage at any time during the experiment. In addition to reducing the leakage of 51Cr-EDTA into the gastric lumen, SOD, catalase, and PGE2 significantly reduced the extent of macroscopically visible mucosal damage (P less than 0.05). These results support the hypothesis that oxygen-derived free radicals, probably derived from neutrophils, contribute to the pathogenesis of Indo-induced ulceration.

Topics: Allopurinol; Animals; Catalase; Chromium Radioisotopes; Deferoxamine; Free Radical Scavengers; Free Radicals; Gastric Mucosa; Hydrochloric Acid; Indomethacin; Male; Oxygen; Rats; Rats, Inbred Strains; Stomach Ulcer; Superoxide Dismutase

We evaluated the role of oxygen free radicals in the induction of acute stress gastric ulcer in rats. After 12 hr of immobility, ulcers of up to 4 mm were observed in the gastric mucosa. Pretreatment with allopurinol, a xanthine oxidase inhibitor, produced a significant reduction in the number and size of lesions (p < 0.0001). No protection was afforded by aluminum hydroxide or ranitidine alone, but enhanced protection was observed when given in association to allopurinol. A secondary role for H ions is suggested by these findings. Our results support the hypothesis of a role of oxygen free radicals in the pathogenesis of stress gastric ulcers. Allopurinol might be used in conditions predisposing to stress in patients.

Topics: Acute Disease; Allopurinol; Aluminum Hydroxide; Animals; Drug Evaluation, Preclinical; Drug Therapy, Combination; Female; Free Radicals; Male; Oxygen Consumption; Ranitidine; Rats; Rats, Sprague-Dawley; Restraint, Physical; Stomach Ulcer; Stress, Physiological

Topics: Animals; Blood Pressure; Cholesterol; Gastric Mucosa; Lipid Peroxidation; Male; Neutrophils; p-Methoxy-N-methylphenethylamine; Rats; Rats, Inbred Strains; Regional Blood Flow; Stomach Ulcer; Superoxides; Vitamin E; Xanthine Oxidase; Xanthines; Zymosan

Oxygen-derived free radicals are cytotoxic and mediate tissue damage. Allopurinol prevents the formation of superoxide radicals and dimethyl sulphoxide (DMSO) scavenges the hydroxyl ones. Intraperitoneal reserpine (5 mg/kg every day for 5 days) produced chronic gastric ulceration in all rats after 4 weeks. Animals gavaged with 1 ml/day of each of 1% allopurinol and 1% DMSO for 4 weeks developed ulceration in 60% of cases; however this ulceration developed in only 20% of animals similarly gavaged with 2% solutions. Rats gavaged with 1 ml/day of each of 5% allopurinol and 5% DMSO for 4 weeks were completely protected against the reserpine-induced chronic gastric ulceration. This protection was not associated with any significant effect on the H+ output of the rat stomach. The results suggest that in the rat, oxygen-derived free radicals are responsible for the development of chronic gastric ulceration and that removing these radicals protects against the said ulceration without influencing acid secretion, i.e. cytoprotection.

Topics: Allopurinol; Animals; Chronic Disease; Dimethyl Sulfoxide; Female; Free Radicals; Gastric Acid; Hydroxides; Hydroxyl Radical; Male; Rats; Rats, Inbred Strains; Reserpine; Stomach Ulcer; Superoxides

This study was designed to determine whether oxygen-derived free radicals play a role in the pathogenesis of gastric lesions produced by hemorrhagic shock in the rat. Allopurinol (Zyloric), an inhibitor of xanthine oxidase (responsible for the formation of superoxide radicals) and MTDQ-DA (Kontrad), a synthetic antioxidant of dihydroquinoline type were used. In the anesthetized rat 0.1 N HCl was instilled into the stomach and the rat was bled to reduce the blood pressure to 30 mmHg for 20 min. The blood shed was retransfused. Twenty min later the stomach was removed. The area of gastric mucosal lesions were measured, the activity of endogenous peroxidase was examined histochemically and a histological grading was made. Both allopurinol and MTDQ-DA significantly protected against hemorrhagic shock-induced gastric lesions and peroxidation. These results suggest that oxygen-derived free radicals play an important role in the formation of gastric lesions produced by ischemia plus 0.1 N HCl.

Topics: Allopurinol; Animals; Antioxidants; Free Radicals; Gastric Mucosa; Male; Oxygen; Quinolines; Rats; Rats, Inbred Strains; Shock, Hemorrhagic; Stomach Ulcer

Acute gastric stress ulceration was induced in rats by cold restraint and was not associated with alteration of gastric pH or serum gastrin level. Cimetidine and oral and intravenous allopurinol were prophylactic but allopurinol was more effective in reducing the depth of the lesion and acted without alteration in gastric pH. The efficacy of allopurinol in preventing stress ulceration offers further indirect evidence of the role of ischaemia and oxygen free radical generation in the aetiology of stress ulceration.

Topics: Allopurinol; Animals; Gastric Acid; Male; Rats; Rats, Inbred Strains; Secretory Rate; Stomach Ulcer; Stress, Psychological

Stress and allopurinol (ALL) were investigated in rats with regard to their influence on serum uric acid and glucose concentration, gastric secretion, microcirculation (MBF) and stress ulcer index. There is a non-competitive type of interaction between severe stress and ALL-mediated xanthine oxydase inhibition (= per cent fall in serum uric acid) as compared with control conditions (= mild stress). Vmax is different (84.6 +/- 1.9 and 92.3+/-2.26; P less than 0.05), but not Km (0.39 +/- 0.09 and 0.68 +/- 0.08 mg/kg/h ALL). Serum uric acid is higher in rats with draining gastric fistula than those with closed fistula suggesting that already mild stress is associated with an increase in uricemia in this species. ALL does not significantly alter gastric acid and uric acid secretion but improves markedly gastric ulcer index during mild and severe stress. Since MBF is significantly elevated by ALL during the latter circumstances, a dissociation between MBF and acid secretion is one feature of ALL actions and might become a primary aim in treatment of this disorder.

Topics: Allopurinol; Animals; Gastric Juice; Humans; Male; Microcirculation; Rats; Stomach; Stomach Ulcer; Stress, Psychological; Uric Acid