A novel antiulcerogenic stable radical prevents gastric mucosal lesions in rats.
The pathogenesis of gastric mucosal injury is still poorly understood. Recent reports implicate redox active metals and reactive oxygen species as mediators of gastric damage induced by ethanol or non-steroidal anti-inflammatory drugs. Attempts were made therefore to prevent gastric injury using chelators and the antioxidant enzymes catalase and superoxide dismutase. These attempts, at best, would only detoxify extracellular reactive species, such as those produced by activated circulating granulocytes and macrophages. This study utilises another strategy by pre-emption of both intra and extracellular reactive species using radical-radical annihilation reactions and by detoxifying redox active transition metals. Nitroxide, stable free radicals were shown to enter mucous cells, protect against the ethanol induced damage, and prevent gastric lesions induced by aspirin, indomethacin, 25% NaCl, or 0.6 N HCl. These findings confirm that gastric mucosal damage from the above agents is mediated by free radicals and, moreover, introduce a prototypical agent within a potential new class of gastric ulcer preventing drugs.
Department of Medicine, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel.
D
D
Rachmilewitz
F
F
Karmeli
E
E
Okon
A
A
Samuni
D000818:Animals; D001241:Aspirin; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D004578:Electron Spin Resonance Spectroscopy; D000431:Ethanol; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D006851:Hydrochloric Acid; D007213:Indomethacin; D015289:Leukotrienes / Q000032:analysis; D008297:Male; D011500:Protein Synthesis Inhibitors / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride; D013113:Spin Labels; D013276:Stomach Ulcer / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors*
D003497:Cyclic N-Oxides; D015289:Leukotrienes; D011500:Protein Synthesis Inhibitors; D013113:Spin Labels; D000431:Ethanol; D012965:Sodium Chloride; D013482:Superoxide Dismutase; D006851:Hydrochloric Acid; D001241:Aspirin; C001803:tempol; D007213:Indomethacin