title: Role of reactive oxygen metabolites in aspirin-induced gastric damage in humans: gastroprotection by vitamin C.
abstract: BACKGROUND
  The roles of active oxygen metabolites and anti-oxidative defenses in aspirin (ASA)-induced gastric damage have been little studied.
  
  
  OBJECTIVE
  We determined the effects of aspirin (400 mg b.d.) with or without vitamin C (480 mg b.d.) for 3 days on gastric mucosa in human volunteers.
  
  
  METHODS
  Gastric injury was assessed endoscopically; gastric blood flow, reactive oxygen release (quantified by chemiluminescence), lipid peroxidation, myeloperoxidase, superoxide dismutase and glutathione peroxidase activity and intragastric vitamin C content were measured. Expression of superoxide dismutase and glutathione peroxidase mRNAs was assayed semi-quantitatively.
  
  
  RESULTS
  ASA produced erosions, a marked increase in chemiluminescence, lipid peroxidation, and myeloperoxidase activity. It also resulted in a suppression of gastric blood flow, intragastric vitamin C levels, superoxide dismutase and glutathione peroxidase activities. The addition of vitamin C significantly attenuated gastric damage and reversed the effects of ASA on these parameters. Superoxide dismutase and glutathione peroxidase mRNAs were decreased in ASA-treated subjects; the addition of vitamin C restored their regular levels.
  
  
  CONCLUSIONS
  (i) free radical-induced lipid peroxidation and suppression of antioxidizing enzymes play an important role in gastric damage induced by aspirin; (ii) increased myeloperoxidase activity suggests activated neutrophils to be the major source of these radicals; (iii) vitamin C protects against ASA-induced damage due to its anti-oxidizing activity.
authors.affiliation: Department of Medicine B, University of Münster, Münster, Germany. pohley@uni-muenster.de
authors.forename: T
authors.initials: T
authors.lastname: Pohle
authors.forename: T
authors.initials: T
authors.lastname: Brzozowski
authors.forename: J C
authors.initials: JC
authors.lastname: Becker
authors.forename: I R
authors.initials: IR
authors.lastname: Van der Voort
authors.forename: A
authors.initials: A
authors.lastname: Markmann
authors.forename: S J
authors.initials: SJ
authors.lastname: Konturek
authors.forename: A
authors.initials: A
authors.lastname: Moniczewski
authors.forename: W
authors.initials: W
authors.lastname: Domschke
authors.forename: J W
authors.initials: JW
authors.lastname: Konturek
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry; D001205:Ascorbic Acid / Q000494:pharmacology*; D001241:Aspirin / Q000008:administration & dosage* / Q000737:chemistry; D015415:Biomarkers; D005260:Female; D005609:Free Radicals; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology*; D005979:Glutathione Peroxidase / Q000096:biosynthesis; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000032:analysis; D017382:Reactive Oxygen Species; D013270:Stomach / Q000187:drug effects / Q000473:pathology*; D013482:Superoxide Dismutase / Q000096:biosynthesis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D005609:Free Radicals; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D001205:Ascorbic Acid; D001241:Aspirin