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.
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Authors | Y Naito, T Yoshikawa, K Matsuyama, N Yagi, Y Nakamura, S Nishimura, T Kaneko, N Yoshida, M Kondo |
Journal | Arzneimittel-Forschung
(Arzneimittelforschung)
Vol. 47
Issue 7
Pg. 845-8
(Jul 1997)
ISSN: 0004-4172 [Print] Germany |
PMID | 9272243
(Publication Type: Journal Article)
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Chemical References |
- Anti-Ulcer Agents
- Free Radical Scavengers
- Guanidines
- Histamine H2 Antagonists
- Lipid Peroxides
- Sulfones
- Thiobarbituric Acid Reactive Substances
- Superoxides
- T 593
- Hydroxyl Radical
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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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