allopurinol and Ulcer

Topics: Adolescent; Adult; Allopurinol; Antimetabolites, Antineoplastic; Brazil; Child; Evaluation Studies as Topic; Follow-Up Studies; Humans; Leishmaniasis, Cutaneous; Meglumine; Middle Aged; Mucous Membrane; Treatment Outcome; Ulcer; Uric Acid

Rats receiving intracolonic administration of indomethacin develop longitudinal ulcers on the mesenteric side of the small intestine that are similar to those seen in the acute phase of Crohn's disease. To investigate the causative role of microcirculatory disturbances and to elucidate the therapeutic effect of antioxidants on this enteropathy in rats, we serially evaluated changes in regional blood flow of the small intestine using laser Doppler perfusion imaging and the colored microsphere injection method. Both methods disclosed stepwise hyperperfusion limited to the mesenteric side of the small intestine following transient ischemia during the initial 30-60 minutes. In addition, both a radical scavenger and a radical production inhibitor significantly ameliorated the mesenteric longitudinal ulcers. We concluded that ischemia-reperfusion on the mesenteric side accompanying excessive production of radicals might be strongly involved in indomethacin-induced longitudinal ulcers of the small intestine in rats.

Topics: Allopurinol; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antipyrine; Cytokines; Disease Models, Animal; Disease Progression; Edaravone; Enzyme-Linked Immunosorbent Assay; Free Radical Scavengers; Ileal Diseases; Ileum; Indomethacin; Laser-Doppler Flowmetry; Male; Mesentery; Microcirculation; Peroxidase; Rats; Rats, Wistar; Regional Blood Flow; Ulcer

Gastrointestinal damage and bleeding are the major side effects of non-steroidal anti-inflammatory drugs (NSAID), however the mechanisms of this ulcerogenic action are not fully understood. It has recently been proposed that neutrophil-and oxygen radical-dependent microvascular injuries may be important prime events that lead to mucosal injury. In addition, other factors like bile flow, intact bacterial flora or feeding conditions may contribute to the formation of lesions. Ketoprofen is a NSAID that exists as a pair of R(-) and S (+) enantiomers; like other 2-arylpropionic acids, its anti-inflammatory effects resides almost exclusively in the S (+) isomer. The present study was undertaken to explore the role of oxidative stress in the pathogenesis of intestinal injury induced by oral administration of racemic ketoprofen and its enantiomers given as their water soluble tromethamine salts.. Evaluation of intestinal damage and activities of oxidative stress related enzymes such as myeloperoxidase (MPO), xanthine-oxidase (XO) and superoxide dismutase (SOD) were studied in an experimental animal model using refed rats.. After the oral treatment followed by a refeeding period of 24 h, ketoprofen (100, 50, 25 mg/Kg b.w.) dose-dependently caused longitudinal ulcers on the mesenteric side of the middle and lower intestine lumen. The intestinal toxicity caused by S(+)-ketoprofen was significantly lower than the effect observed after racemate and R(-) enantiomer treatments (P <0.001), though the bioinversion of R(-)-ketoprofen to S(+)-enantiomer that occurs in the rat has to be considered. XO activity was unaffected by the studied drugs. Enhanced enteropathy by the racemate and its R (-)-enantiomer was correlated with a significant increase of MPO activity as an index of neutrophil infiltration, and a decrease in SOD activity (p<0.05 Vs control). S(+)-ketoprofen did not significantly change these parameters.. These results suggest that reactive oxygen metabolites can contribute significantly to the development of intestinal lesions, and that R(-)-ketoprofen present in racemic preparations can enhance the toxic intestinal effects of S (+)-enantiomer via modification of neutrophil migration and oxidative stress.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Intestinal Diseases; Intestinal Mucosa; Ketoprofen; Male; Neutrophil Infiltration; Oxidative Stress; Peroxidase; Rats; Rats, Wistar; Stereoisomerism; Superoxide Dismutase; Tromethamine; Ulcer; Xanthine Oxidase

Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used and may cause small intestinal inflammation and damage. Reactive oxygen metabolites are involved in various gastrointestinal inflammatory processes, but there is little information about their role in small intestinal mucosal damage induced by NSAIDs. We studied the effect of the oxygen radical scavengers superoxide dismutase (SOD), catalase (CAT), and allopurinol (ALLO) on indomethacin (INDO)-induced intestinal ulceration in the rat. Ulceration was produced by s.c. injection of 30 mg/kg of INDO 30 min after refeeding 24 h-fasted rats. Total ulcer area was measured 24 h after INDO administration. Study groups each consisted of eight animals which received either i.p. CAT, SOD, or both together, at a dosage of 5,000 U/kg each. All drugs were divided into five doses, given once an hour over a 4-h period, starting at the time of INDO injection. Another group received 100 mg/kg ALLO in two doses. Total ulcer area was reduced by SOD from 228 +/- 12 (sq mm, mean +/- SEM) to 153 +/- 12 (p < 0.001), by CAT to 179 +/- 13 (p < 0.01), and by both together to 95 +/- 5 (p < 0.0001). ALLO administration reduced the total ulcer area to 176 +/- 7 (p < 0.003). The protective effect of oxyradical scavengers supports the hypothesis that oxygen radicals are involved in the pathogenesis of INDO-induced small intestinal ulceration in the rat.

Topics: Allopurinol; Animals; Anti-Inflammatory Agents, Non-Steroidal; Catalase; Free Radical Scavengers; Indomethacin; Intestinal Diseases; Male; Rats; Rats, Wistar; Superoxide Dismutase; Ulcer

Three cases of oral lichenoid reaction linked with the administration of allopurinol are presented. Withdrawal of the drug resulted in considerable clinical improvement in one case and complete resolution of the ulcerative lesions in the other two cases. The consideration of drug-induced reactions in the differential diagnosis of oral mucosal diseases has been emphasized.

Topics: Allopurinol; Cheek; Humans; Lichen Planus; Male; Middle Aged; Mouth Diseases; Mouth Mucosa; Tongue Diseases; Ulcer

Topics: Allopurinol; Diagnosis, Differential; Female; Humans; Middle Aged; Mouth Diseases; Stevens-Johnson Syndrome; Ulcer