allopurinol and Peptic-Ulcer

This study investigated whether the free radical scavengers allopurinol (50 mg p.o. q.i.d.) and dimethyl sulphoxide (DMSO, 500 mg p.o. q.i.d.) influence the incidence of stress-induced acute gastric mucosal injury in patients with pelvic fractures and hypovolaemic shock. In 177 fully evaluable patients (control n = 58, allopurinol n = 62, DMSO n = 57), endoscopically proven stress-induced injury evolved in a significantly (p less than 0.01) larger number of controls relative to either group on active therapy. During the first 3 days after hospitalization, 13 controls (22%) developed the injury whereas only 2 patients in each of the allopurinol (3%) and DMSO (4%) groups had this injury. Of these cases, 8 controls (14%) and one patient in the allopurinol group (2%) deteriorated and underwent emergency surgery, however 3 of the controls (5%) died in the immediate post-operative period. The results suggest that oxygen-derived free radicals are directly implicated in stress-induced acute gastric mucosal injury and that removing them protects against this injury and its complications.

Topics: Adolescent; Adult; Aged; Allopurinol; Dimethyl Sulfoxide; Double-Blind Method; Female; Fractures, Bone; Free Radicals; Gastric Mucosa; Humans; Male; Middle Aged; Pelvic Bones; Peptic Ulcer; Prognosis; Prospective Studies; Shock

We investigated the role of xanthine oxidase-derived oxygen radicals in the development of endothelin-1-induced gastric ulcer. Mucosal lipid peroxidation showed a peak 24 h after injection, while gastric mucosal haemodynamics were fully restored 26 h after endothelin-1 injection. Allopurinol and oxypurinol, but not superoxide dismutase or catalase, protected the gastric mucosa 24 h after endothelin-1 injection. Oxypurinol antagonized both the vasoconstrictor effect of endothelin-1 and the decrease in gastric ATP. All treatments on the second day after endothelin-1 injection significantly reduced gastric mucosal damage. Xanthine oxidase-derived oxygen radicals contributed largely to the exacerbation but they did not mediate the onset of endothelin-1-induced gastric ulcer. Pretreatment with probucol (500 mg/kg, p.o.) also protected the gastric mucosa from endothelin-1-induced mucosal injury by its antioxidant activity. Oxypurinol was gastroprotective through its vasoactive and energy saving actions. The haemodynamic background of endothelin-1-induced gastric ulcer consists of long lasting ischaemia and subsequent "reperfusion" which may be responsible for the late burst of oxygen radicals.

Topics: Adenosine Triphosphate; Aldehydes; Allopurinol; Animals; Catalase; Deferoxamine; Disease Progression; Endothelin-1; Gastric Mucosa; Male; Malondialdehyde; Oxypurinol; Peptic Ulcer; Probucol; Rats; Rats, Wistar; Regional Blood Flow; Superoxide Dismutase; Superoxides; Vasoconstriction; Xanthine Oxidase

Cigarette smoking has been associated with peptic ulcer diseases. We studied the effects of cigarette smoke exposure on ethanol-induced gastric mucosal damage and its relationship with vascular integrity and the possible role of free radicals and histamine. Male Sprague-Dawley rats were exposed to cigarette smoke followed by ethanol administration (70% v/v). Smoke exposure alone dose-dependently reduced basal blood flow and increased xanthine oxidase (XO) activity but superoxide dismutase (SOD) activity remained unaffected in gastric mucosa. Cigarette smoking followed by ethanol administration significantly potentiated mucosal lesion formation along with augmentation of the mucosal blood flow, vascular permeability and myeloperoxidase (MPO) activity. The potentiating effect of smoking on ethanol-induced gastric mucosal lesion and MPO activity was abolished by pretreatment with allopurinol, terfenadine or ranitidine. Terfenadine and ranitidine also reduced the increased mucosal blood flow and vascular permeability induced by smoking and ethanol combined. These findings suggested that cigarette smoke adversely affected the defense mechanisms of the gastric mucosa by reducing the mucosal blood flow which in turn led to ischemia and increased XO activity. Activation of XO together with histamine H1 and H2 receptors stimulation could lead to neutrophil aggregation and vascular damage. However, the potentiating action of cigarette smoke on ethanol ulceration is unlikely through reduction of SOD activity in gastric mucosa.

Topics: Animals; Disease Models, Animal; Ethanol; Free Radicals; Gastric Mucosa; Histamine; Histamine H1 Antagonists; Histamine H2 Antagonists; Male; Peptic Ulcer; Peroxidase; Ranitidine; Rats; Rats, Sprague-Dawley; Smoking; Superoxide Dismutase; Terfenadine; Xanthine Oxidase

The relationship between Helicobacter pylori (H. pylori), xanthine oxidase (XO)-induced oxygen derived free radicals (ODFR) and histamine in the induction of human gastroduodenal disorders was investigated.. Histamine concentration, XO and xanthine dehydrogenase (XD) activities were measured in endoscopically obtained biopsies from 66 symptomatic patients.. H. pylori infection was associated with lower oxyntic and duodenal histamine in 'normal' controls (group N) (p < 0.002 and p < 0.05, respectively). Patients with gastroduodenal disease tended to have reduced mucosal concentration of histamine, but comparing H. pylori positive and negative patients, infection did not lead to a further fall in histamine concentration. H. pylori positive duodenal ulcer (DU) patients tended to have higher XO activity than group N (p = 0.051) and had a significantly lowered activity of XD, the precursor of XO (p' < 0.05). Histamine concentration at the ulcer-edge was lower while XO activity was higher than in the distant normal mucosa (p < 0.05, respectively). Gastritis (group GL) with H. pylori also had lower XD than H. pylori positive group N (p' < 0.025) but no corresponding rise in XO activity. In group N, duodenal mucosal histamine and XD activity were inversely related (Rs = -0.51, p < 0.025).. These findings support the hypothesis that histamine, xanthine oxidase related ODFR, and H. pylori may be closely associated in the manifestations of chronic duodenal ulcer.

Topics: Adult; Aged; Endoscopy; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Histamine; Humans; Intestinal Mucosa; Male; Middle Aged; Peptic Ulcer; Reactive Oxygen Species; Xanthine Dehydrogenase; Xanthine Oxidase

Refractory peptic ulceration refers to ulcers which are slow to heal despite active treatment for at least three months. Oxygen-derived free radicals are cytotoxic and promote tissue injury. Twelve consecutive patients with refractory peptic ulceration (eight with duodenal ulcers and four with solitary pre-pyloric gastric ulcers) were treated using the radical scavengers allopurinol or dimethyl sulphoxide. This treatment was well tolerated by all patients and produced no adverse effects. Endoscopic examination four weeks later demonstrated complete healing (an intact gastric or duodenal mucosa without any breaches) in all patients. The results suggest that oxygen-derived free radicals perpetuate the process of peptic ulceration and exert an adverse effect on healing. Scavengers of these radicals stimulate the healing of refractory gastric and duodenal ulceration.

Topics: Adult; Allopurinol; Cimetidine; Dimethyl Sulfoxide; Female; Free Radical Scavengers; Free Radicals; Humans; Male; Middle Aged; Peptic Ulcer

Topics: Allopurinol; Dimethyl Sulfoxide; Humans; Intensive Care Units; Peptic Ulcer; Stress, Psychological

Stress ulceration is frequently encountered after cardiovascular surgery. In this study of 32 male baboons, severe gastric ischaemia was used to produce gastric stress lesions. The occurrence of these lesions was reduced by allopurinol (P = 0.03) and completely prevented by the combination of allopurinol with superoxide dismutase (P = 0.004). A shorter ischaemic period also reduced the number of lesions (P = 0.02). Concurrent with the stress lesion formation, there was a fall in mucosal glutathione and oxidized glutathione levels (P less than 0.05).

Topics: Allopurinol; Animals; Disease Models, Animal; Gastric Mucosa; Ischemia; Male; Papio; Peptic Ulcer; Stress, Physiological; Superoxide Dismutase

Topics: Adult; Aged; Biopsy; Chemical Phenomena; Chemistry; Cholecystitis; Female; Humans; Liver; Male; Methylene Blue; Middle Aged; NAD; Oxygen; Peptic Ulcer; Temperature; Time Factors; Trypsin; Xanthine Oxidase; Xanthines