title: Effect of allopurinol, sulphasalazine, and vitamin C on aspirin induced gastroduodenal injury in human volunteers.
abstract: BACKGROUND
  The mechanisms of aspirin induced gastroduodenal injury are not fully understood. Aspirin induces the release of reactive oxygen metabolites in animal models, which may contribute to mucosal injury.
  
  
  OBJECTIVE
  To investigate the effects of aspirin administered with placebo or antioxidants on gastric mucosal reactive oxygen metabolite release and gastroduodenal injury in human volunteers.
  
  
  METHODS
  Fourteen healthy volunteers participated in the study (seven male; mean age 27 years, range 20-40).
  
  
  METHODS
  In a double blind, randomised, crossover study, volunteers received aspirin 900 mg twice daily and either placebo, allopurinol 100 mg twice daily, sulphasalazine 1 g twice daily or vitamin C 1 g twice daily for three days. Injury was assessed endoscopically and by quantifying mucosal reactive oxygen metabolite release by measuring chemiluminescence before and after each treatment. The effect on prostanoids was determined by measuring ex vivo antral prostaglandin E2 (PGE2) synthesis and serum thromboxane B2 (TXB2).
  
  
  RESULTS
  No drug reduced any parameter of gastric injury but vitamin C reduced duodenal injury assessed by Lanza score (p < 0.005). Chemiluminescence increased after aspirin both with placebo (p < 0.05) and vitamin C (p < 0.05). Post-treatment chemiluminescence was lower in subjects taking allopurinol (p < 0.05) or sulphasalazine (p < 0.005) than in those taking placebo with aspirin.
  
  
  CONCLUSIONS
  In this study, aspirin induced gastric injury was associated with reactive oxygen metabolite release. This was reduced by sulphasalazine and allopurinol, although macroscopic injury was not affected. Vitamin C, however, was shown to have a previously unrecognised protective effect against aspirin induced duodenal injury.
authors.affiliation: Division of Gastroenterology, University Hospital, Nottingham.
authors.forename: M E
authors.initials: ME
authors.lastname: McAlindon
authors.forename: A F
authors.initials: AF
authors.lastname: Muller
authors.forename: B
authors.initials: B
authors.lastname: Filipowicz
authors.forename: C J
authors.initials: CJ
authors.lastname: Hawkey
mesh_terms: D000328:Adult; D000493:Allopurinol / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001241:Aspirin / Q000009:adverse effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004381:Duodenal Ulcer / Q000139:chemically induced; D004386:Duodenum / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D008297:Male; D011458:Prostaglandins E / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012460:Sulfasalazine / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D000975:Antioxidants; D011458:Prostaglandins E; D017382:Reactive Oxygen Species; D012460:Sulfasalazine; D000493:Allopurinol; D001205:Ascorbic Acid; D001241:Aspirin