A novel antiulcerogenic stable radical prevents gastric mucosal lesions in rats.

Abstract

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 extraceliular 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 HCI.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.

Noninvasive Mapping of Reactive Oxygen Species by in Vivo Electron Spin Resonance Spectroscopy in Indomethacin-Induced Gastric Ulcers in Rats

“…The arrow in B indicates the hemorrhage caused by indomethacin treatment. jpet.aspetjournals.org mg/kg) completely prevented the ulcer formation (Rachmilewitz et al, 1994). In this study, not only hydroxy-TEMPO but also other nitroxyl probes with different Po/w values were evaluated, and the evidence that carboxy-and trimethylammonium-TEMPO with relatively low Po/w values had no effect on the ulcer formation shows, for the first time, that the sites of accumulation of antioxidants are critical in protecting against gastric ulcers.…”

Antioxidative Properties of Pig Vesical Mucosa: A Comparison with Gastric and Intestinal Mucosa.

“…The gastric, intestinal, and bladder-scraped mucosal area needed for achieving the 500 ml of the surface layer homogenates, ranged from 5-7.5 cm 2 , 10-15 cm 2 , and 70-110 cm 2 , respectively. The obtained samples were homogenized with the Potter-Elvehjem homogenizer or vigorously stirred on vortex (the results obtained by both methods did not differ significantly).…”

Rutoxyl [rutin/4‐acetamide‐1‐hydroxy‐2,2,6,6‐tetramethylpiperidinium] is a new member of the class of semi‐natural products of high pharmacological potency

“…It is known recently (5) that nitroxide undergoes chemical and/or cellular reduction to the corresponding one-electron reduced nitroxylamine ()N----OH), which is oxidized back to the nitroxide by various oxidants (chemical of cellular). However, cellular oxidation of nitroxylamine will depend on many factors which include the oxygen tension, the level of ROS and/or the redox status of the cell (3)(4)(5). In biological systems, in vivo, there probably exists an equilibrium between nitroxide and its corresponding nitroxylamine derivative (3)(4)(5).…”

“…Nitroxides are subject to steric hindrance, but the fully substitution in the orthoposition inhibits their dismutation thus rendering them stable free radicals which can terminate other radical(s) chain reactions (4,5). It is known recently (5) that nitroxide undergoes chemical and/or cellular reduction to the corresponding one-electron reduced nitroxylamine ()N----OH), which is oxidized back to the nitroxide by various oxidants (chemical of cellular).…”