allopurinol and Gastrointestinal-Hemorrhage

Review the histologic and pathophysiologic alterations seen after intestinal ischemia and reperfusion.. Current literature review.. The most pertinent, current, and representative articles describing results from both animal and human investigations are utilized and discussed.. Postischemic intestinal tissue damage appears to be due to the formation of oxygen radicals and the activation of phospholipase A2. The initial source of oxygen radicals seems to be the hypoxanthine-xanthine oxidase system. Oxygen radicals react directly with poly-unsaturated fatty acids, leading to lipid peroxidation within the cell membranes. Indirectly, the radicals trigger the accumulation of neutrophils within the affected tissue initiating inflammatory processes that lead to severe mucosal lesions. Similarly, phospholipase A2 also initiates postischemic mucosal lesions. Phospholipase A2 is a hydrolytic enzyme capable of increasing formation of cytotoxic lysophospholipids within the tissue. Enhanced activity of phospholipase A2 also stimulates the production of prostaglandins and leukotrienes. Various substances (superoxide dismutase, catalase, dimethyl sulfoxide, allopurinol, and deferoxamine, etc.) are able to detoxify oxygen radicals or inhibit the mechanisms leading to their enhanced generation, thus attenuating the postischemic lesions of the mucosa.. Oxygen radicals and the activation of phospholipase A2 during reperfusion seem to be instrumental for the development of hemorrhagic mucosal lesions after intestinal ischemia. Radical scavengers and phospholipase A2 inhibitors may prevent reperfusion damage of the intestine, even when the treatment starts during ischemia but before reperfusion.

Topics: Animals; Antioxidants; Cats; Disease Models, Animal; Free Radical Scavengers; Free Radicals; Gangrene; Gastrointestinal Hemorrhage; Humans; Hypoxanthines; Inflammation; Intestines; Leukotrienes; Lipid Peroxidation; Neutrophils; Phospholipases A; Phospholipases A2; Prostaglandins; Rats; Reactive Oxygen Species; Reperfusion Injury; Xanthine Oxidase

Topics: Adult; Aged; Allopurinol; Dimethyl Sulfoxide; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe adverse drug reactions with high mortality. The use of corticosteroids and the management of complications (e.g. infection) in SJS/TEN remains controversial.. A retrospective study was performed among 213 patients with SJS/TEN who were hospitalized in our department between 2008 and 2018, to investigate the causative agents, clinical characteristics, complications, and prognoses of SJS/TEN mainly treated by systemic corticosteroids combined with intravenous immunoglobulin (IVIG).. The causative drugs of SJS/TEN in these patients mainly consisted of antibiotics (61/213, 28.6%), anticonvulsants (52/213, 24.4%), and nonsteroidal anti-inflammation drugs (24/213, 11.3%), among which carbamazepine was the most frequently administered drug (39/213, 18.3%). There were significant differences in the maximum dosage, time to corticosteroid tapering, and the total dosage of corticosteroid between the SJS group and the TEN group, as well as among the three groups (P = 0.000), whereas in the initial dose of corticosteroid was not statistically significant among the three groups (P = 0.277). In a series of 213 cases, 18.4 cases (8.6%) were expected to die based on the score for the toxic epidermal necrolysis (SCORTEN) system, whereas eight deaths (3.8%) were observed; the difference was not statistically significant (P = 0.067; SMR = 0.43, 95% CI: 0.06, 0.48). The most common complications were electrolyte disturbance (174/213, 81.7%), drug-induced liver injury (64/213, 30.0%), infection (53/213, 24.9%), and fasting blood sugar above 10 mmol/L (33/213, 15.5%). Respiratory system (22/213, 10.3%) and wound (11/213, 5.2%) were the most common sites of infection. Multivariate logistic regression analysis indicated that the maximum blood sugar (≥10 mmol/L), the time to corticosteroid tapering (≥12 d), the maximum dosage of corticosteroid (≥1.5 mg/kg/d), and the total body surface area (TBSA) (≥10%) were defined as the most relevant factors of the infection.. The mortality of patients in this study was lower than that predicted by SCORTEN, although there was no significant difference between them. Hyperglycemia, high-dose corticosteroid, and the TBSA were closely related to the infections of patients with SJS/TEN.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Allopurinol; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Blood Glucose; Body Surface Area; Chemical and Drug Induced Liver Injury; China; Cohort Studies; Drugs, Chinese Herbal; Female; Gastrointestinal Hemorrhage; Glucocorticoids; Gout Suppressants; Humans; Hyperglycemia; Hypertension; Immunoglobulins, Intravenous; Immunologic Factors; Klebsiella Infections; Male; Middle Aged; Pneumonia; Pulmonary Aspergillosis; Respiratory Tract Infections; Retrospective Studies; Risk Factors; Stevens-Johnson Syndrome; Survival Rate; Water-Electrolyte Imbalance; Wound Infection

To investigate the role of gastric oxidative stress and nitric oxide (NO) in the formation of gastric hemorrhagic erosion and their protection by drugs in rats with ischemic brain.. Male Wistar rats were deprived of food for 24 h. Under chloral hydrate (300 mg/kg) anesthesia, bilateral carotid artery ligation was performed. The pylorus and carotid esophagus of the rats were also ligated. The stomachs were then irrigated for 3 h with either normal saline or simulated gastric juice containing 100 mmol/L HCl plus 17.4 mmol/L pepsin and 54 mmol/L NaCl. Rats were killed and stomachs were dissected. Gastric mucosa and gastric contents were harvested. The rat brain was dissected for the examination of ischemia by triphenyltetrazolium chloride staining method. Changes in gastric ulcerogenic parameters, such as decreased mucosal glutathione level as well as enhanced gastric acid back-diffusion, mucosal lipid peroxide generation, histamine concentration, luminal hemoglobin content and mucosal erosion in gastric samples, were measured.. Bilateral carotid artery ligation produced severe brain ischemia (BI) in rats. An exacerbation of various ulcerogenic parameters and mucosal hemorrhagic erosions were observed in these rats. The exacerbated ulcerogenic parameters were significantly (P<0.05) attenuated by antioxidants, such as exogenous glutathione and allopurinol. These gastric parameters were also improved by intraperitoneal aminoguanidine (100mg/kg) but were aggravated by N(G)-nitro-L-arginine-methyl ester (L-NAME: 25 mg/kg). Intraperitoneal L-arginine (0-500 mg/kg) dose-dependently attenuated BI-induced aggravation of ulcerogenic parameters and hemorrhagic erosions that were reversed by L-NAME.. BI could produce hemorrhagic erosions through gastric oxidative stress and activation of arginine-nitric oxide pathway.

Topics: Allopurinol; Animals; Arginine; Brain Ischemia; Gastric Mucosa; Gastrointestinal Hemorrhage; Glutathione; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Oxidative Stress; Rats; Rats, Wistar

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

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

The exposure of gastric mucosa to ethanol produces pathological changes such as inflammatory process, hemorrhagic erosions, even acute ulcers. The gastric mucosal lesions accompanied by a significant decrease of gastric blood flow and increase of reactive oxygen species (ROS) implicate a role of xanthine oxidase in ethanol-induced gastric hemorrhagic erosions. DA-9601, a novel antipeptic formulation of extracts of Artemisia asiatica Nakai, 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. Intubation of absolute ethanol (4 g/kg) significantly induced gastrohemorrhagic lesions and lipid peroxidation in the rat stomach. Oral administration of DA-9601 at 40 mg/kg body weight significantly reduced ethanol-induced gastric mucosal hemorrhagic lesions and lipid peroxidation, which was proportional to the inhibitory effect of DA-9601 on alcohol-induced xanthine oxidase-type conversion and enzyme activity. The results suggest that alcohol-induced gastric mucosal damage may be, in part, due to the increased activity of xanthine oxidase and type conversion rate of the enzyme and that the preventive effect of DA-9601 on gastrohemorrhagic lesions would result from its inhibitory action against xanthine oxidase and oxidative stress in alcohol-treated rats.

Topics: Administration, Oral; Animals; Anti-Ulcer Agents; Artemisia; Enzyme Inhibitors; Ethanol; Gastrointestinal Hemorrhage; Lipid Peroxidation; Male; Plant Extracts; Rats; Rats, Sprague-Dawley; Stomach; Xanthine Oxidase

In addition to a deficiency of endogenous prostaglandins due to inhibition of cyclo-oxygenase and a host of prostaglandin-mediated effects on mucosal protection, it has recently been proposed that neutrophil- and oxygen radical - dependent microvascular injuries may be important prime events that lead to mucosal injury induced by non-steroidal anti-inflammatory drugs. Therefore, we evaluated the role of oxygen free radicals in the pathogenesis of acute gastric ulceration induced by meloxicam, a preferential COX-2 inhibitor.. Studies were performed in Wistar rats.. Meloxicam was given by oral administration (3.75-30 mg/kg body weight).. Determinations were made of gastric mucosal injury, xanthine-oxidase, myeloperoxidase and superoxide dismutase activities, as well as the effect of meloxicam on gastric prostaglandin synthesis (PGE2 levels) and glutathione homeostasis.. Oral administration of meloxicam dose-dependently (3.75-30 mg/kg) caused acute gastric haemorrhage erosions. The total area of gastric lesions increased with time until 24 hours after dosing. Xanthine-oxidase activity increased significantly after administration of the drug. Myeloperoxidase activity, as an index of neutrophil infiltration, as well as glutathione peroxidase, an important enzyme that scavenges lipid peroxides, were unaffected by meloxicam administration. In addition, superoxide dismutase activity, PGE2 and glutathione levels were significantly reduced.. These results support the hypothesis that in addition to suppression of prostaglandin synthesis, oxygen free radicals, probably derived via the action of xanthine oxidase, the decrease in superoxide dismutase activity, and the depletion of mucosal glutathione contribute to the pathogenesis of meloxicam-induced ulceration.

Topics: Animals; Dinoprostone; Female; Free Radicals; Gastric Mucosa; Gastrointestinal Hemorrhage; Glutathione; Glutathione Peroxidase; Male; Meloxicam; Neutrophils; Peroxidase; Rats; Rats, Wistar; Reactive Oxygen Species; Superoxide Dismutase; Thiazines; Thiazoles; Xanthine Oxidase

Rebamipide, 2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinone-4-yl]-propionic acid, a novel antipeptic ulcer agent, has been reported to prevent various acute experimental gastric mucosal lesions and to accelerate the healing of chronic ulcers. Therapeutic effect of rebamipide was investigated with regard to the inhibitory effect on xanthine oxidase activity and type conversion of the enzyme which play a profound role in oxygen radicals generation system. Intraperitoneal administration of rebamipide at 60 mg/kg body weight reduced the xanthine oxidase activity, lipid peroxide content in ammonia induced hemorrhagic lesion. These results suggest that the therapeutic effect of rebamipide on gastric mucosal lesion may be in part due to the inhibitory activity of xanthine oxidase and type conversion rate of the enzyme.

Topics: Alanine; Ammonia; Animals; Anti-Ulcer Agents; Enzyme Inhibitors; Gastric Mucosa; Gastrointestinal Hemorrhage; Lipid Peroxidation; Lipid Peroxides; Male; Quinolones; Rats; Rats, Sprague-Dawley; Xanthine Dehydrogenase; Xanthine Oxidase

Histamine release have been demonstrated in haemorrhagic shock. There are some observations that oxygen free radicals can cause histamine release. Oxygen free radicals play a role in the pathogenesis of gastric mucosal lesions. The goal of this study was to determine whether ranitidine or SOD and allopurinol pretreatment modify the histamine release during and after the haemorrhagic shock in the rat. In the anaesthetized 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 shed blood was reinfused. Twenty min later the stomach was removed. The area of gastric mucosal lesions were measured, histological grading was made. Blood samples taken from the carotid artery were examined by radioimmunoassay (IMMUNOTECH) to determine the plasma histamine level. Plasma histamine level did not change significantly during the preparative surgery, but there was a significant increase of histamine level by the end of shock period. After the reinfusion of the blood the plasma histamine remained essentially at the same level for five min. Oxygen free radicals did not cause an important histamine release. By the end of the experiment the histamine level decreased dramatically. Ranitidine, allopurinol and SOD pretreatment provided significant protection against the gastric mucosal lesions. Allopurinol and SOD did not influence significantly the histamine level. Ranitidine caused significant histamine release immediately after the injection and every histamine value was significantly higher in this group except for the final value which was lower than the control one. The oxygen free radicals were not found as endogenous histamine releasers in this study.

Topics: Allopurinol; Animals; Gastric Mucosa; Gastrointestinal Hemorrhage; Histamine; Histamine Release; Male; Ranitidine; Rats; Rats, Wistar; Shock, Hemorrhagic; Superoxide Dismutase

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

This study was performed to clarify the relationship between hemodynamics, congestive damage, lipid peroxidation and intraluminal hemorrhage of the small intestine. Using 51Cr-red blood cells, with a temporary occlusion of the portal vein for 30 min. in rats, the hemodynamic, biochemical and histological changes were investigated. By occluding the portal vein, its pressure increased to a level eight times higher than normal, and destruction of the intestinal mucosa and an increase of TBA reactants were observed. The intraluminal hemorrhage of the intestine increased to a quantity 7.5 times higher than usual during portal vein occlusion, and it decreased gradually after reperfusion. At 120 min. after reperfusion, this amount remained high, but the administration of Allopurinol diminished its level. A technique of temporary simultaneous occlusion of the superior mesenteric artery or the bypass between the portal and jugular veins was effective in reducing the congestive damage on the intestine. During the occlusion of the portal vein, sudden and high pressure of the portal vein primarily causes congestive damage, and superoxide generated by a xanthine oxidase system during reperfusion may cause lipid peroxidation which induces reperfusion injury. Thus, the lipid peroxidation may accelerate the injury on the small intestine.

Topics: Allopurinol; Animals; Gastrointestinal Hemorrhage; Hemodynamics; Intestine, Small; Lipid Peroxidation; Male; Portal Vein; Rats; Rats, Inbred Strains; Reperfusion Injury

Six days after initiating therapy with allopurinol, toxic epidermal necrolysis developed in a 73-year-old man with renal failure. It was responsible for a generalized vasculitis and gastrointestinal bleeding ultimately leading to death. The authors emphasize the need for a careful evaluation before prescribing this medication, particularly in patients with renal failure.

Topics: Aged; Allopurinol; Epidermolysis Bullosa; Gastrointestinal Hemorrhage; Humans; Kidney Failure, Chronic; Male; Uric Acid; Vasculitis

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

Topics: Aged; Alcoholism; Allopurinol; Arrhythmias, Cardiac; Chloral Hydrate; Colchicine; Digoxin; Drug Synergism; Gastrointestinal Hemorrhage; Gout; Hospitals, Teaching; Humans; Liver Diseases; Male; Middle Aged; Nitroglycerin; Patient Care Team; Pharmacists; Pharmacy Service, Hospital; Quinidine; Warfarin; Washington

Topics: Adolescent; Adult; Aged; Allopurinol; Anaphylaxis; Asparaginase; Blood Coagulation Disorders; Cytarabine; Daunorubicin; Drug Hypersensitivity; Female; Fever; Gastrointestinal Hemorrhage; Hallucinations; Humans; Hyperglycemia; Injections, Intravenous; Jaundice; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Liver; Male; Mercaptopurine; Methotrexate; Middle Aged; Oral Hemorrhage; Prednisone; Thioguanine; Uremia; Vincristine; Vomiting