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Effect of the histamine H2-receptor antagonist (+/-)-(E)-1-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]-3'-[2-[[[5-methylamino ) methyl-2-furyl] methyl]thio]ethyl]-2"-(methylsulfonyl)guanidine on acute gastric mucosal injury in rats and its free-radical scavenging activities.

Abstract
The protective effect of T-593 ((+/-)-(E)-1-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]-3'-[2-[[[5-(methylamino) methyl-2-furyl]methyl]thio]ethyl]-2"-(methylsulfonyl)guanidine, CAS 140695-21-2), a new histamine H2-receptor antagonist, was investigated in rats with acute gastric mucosal injury. An ischemic injury followed by reperfusion was produced by applying a small vascular clamp to the celiac artery for 30 min and then removing it for 60 min. T-593 significantly reduced the area of the lesion in the stomach in a dose-dependent manner, and doses of 0.3 and 3.0 mg/kg inhibited the increase of lipid peroxides in the gastric mucosa after ischemia-reperfusion. A spin-trapping method using 5,5-dimethyl-1-pyrroline-N-oxide showed that T-593 scavenged hydroxyl radicals generated by the hydrogen peroxide-ferrous iron sulfate system. T-593 also significantly inhibited the increase of lipid peroxides induced by free-radical initiators in gastric mucosal homogenates. Thus, the protective effect of T-593 against acute gastric mucosal injury induced by ischemia and followed by reperfusion may result, in part, from its antioxidant properties.
AuthorsY Naito, T Yoshikawa, K Matsuyama, N Yagi, Y Nakamura, S Nishimura, T Kaneko, N Yoshida, M Kondo
JournalArzneimittel-Forschung (Arzneimittelforschung) Vol. 47 Issue 7 Pg. 845-8 (Jul 1997) ISSN: 0004-4172 [Print] Germany
PMID9272243 (Publication Type: Journal Article)
Chemical References
  • Anti-Ulcer Agents
  • Free Radical Scavengers
  • Guanidines
  • Histamine H2 Antagonists
  • Lipid Peroxides
  • Sulfones
  • Thiobarbituric Acid Reactive Substances
  • Superoxides
  • T 593
  • Hydroxyl Radical
Topics
  • Animals
  • Anti-Ulcer Agents (pharmacology, therapeutic use)
  • Free Radical Scavengers (pharmacology, therapeutic use)
  • Gastric Mucosa (blood supply, pathology)
  • Guanidines (pharmacology, therapeutic use)
  • Histamine H2 Antagonists (pharmacology, therapeutic use)
  • Hydroxyl Radical
  • Lipid Peroxides (blood, metabolism)
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Regional Blood Flow (drug effects)
  • Reperfusion Injury (pathology)
  • Stomach Ulcer (pathology, prevention & control)
  • Sulfones (pharmacology, therapeutic use)
  • Superoxides (metabolism)
  • Thiobarbituric Acid Reactive Substances (metabolism)

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