Role of oxygen-derived free radicals in indomethacin-induced gastric injury

Am J Physiol. 1991 Sep;261(3 Pt 1):G470-5. doi: 10.1152/ajpgi.1991.261.3.G470.


The role of oxygen-derived free radicals in the pathogenesis of acute gastric ulceration induced by indomethacin (Indo) was investigated in rats. Gastric damage was assessed by blood-to-lumen leakage of 51Cr-EDTA, as well as by measuring the extent of macroscopically visible hemorrhagic lesions. The stomach was perfused with isotonic saline for 30 min, followed by Indo (10 mg/ml for 30 min) and HCl (100 mM for 60 min). Rats were given a continuous intravenous infusion of the antioxidant enzymes superoxide dismutase (SOD) or catalase or the iron-chelating agent deferoxamine. Additional rats received an intravenous infusion of the vehicle (control group) or were pretreated with prostaglandin E2 (100 micrograms/kg ip) or allopurinol (50 mg/kg po). Exposure of the stomach to Indo caused a fourfold increase in 51Cr-EDTA leakage compared with that observed in rats receiving only the vehicle for Indo. Subsequent exposure of the stomach to HCl resulted in a further twofold increase in 51Cr-EDTA leakage. Treatment with SOD, catalase, or deferoxamine significantly (P less than 0.05) reduced 51Cr-EDTA leakage during the intragastric perfusion with Indo and during the subsequent exposure to HCl. Pretreatment with PGE2 reduced 51Cr-EDTA leakage during perfusion with HCl only. Pretreatment with allopurinol did not significantly affect 51Cr-EDTA leakage at any time during the experiment. In addition to reducing the leakage of 51Cr-EDTA into the gastric lumen, SOD, catalase, and PGE2 significantly reduced the extent of macroscopically visible mucosal damage (P less than 0.05). These results support the hypothesis that oxygen-derived free radicals, probably derived from neutrophils, contribute to the pathogenesis of Indo-induced ulceration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allopurinol / pharmacology
  • Animals
  • Catalase / pharmacology
  • Chromium Radioisotopes
  • Deferoxamine / pharmacology
  • Free Radical Scavengers*
  • Free Radicals
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / physiopathology*
  • Hydrochloric Acid / toxicity
  • Indomethacin / toxicity*
  • Male
  • Oxygen / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Stomach Ulcer / chemically induced
  • Stomach Ulcer / physiopathology*
  • Superoxide Dismutase / pharmacology


  • Chromium Radioisotopes
  • Free Radical Scavengers
  • Free Radicals
  • Allopurinol
  • Catalase
  • Superoxide Dismutase
  • Deferoxamine
  • Hydrochloric Acid
  • Oxygen
  • Indomethacin