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.
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.
Naito
Y
Y
First Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Yoshikawa
T
T
Matsuyama
K
K
Yagi
N
N
Nakamura
Y
Y
Nishimura
S
S
Kaneko
T
T
Yoshida
N
N
Kondo
M
M
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000627:therapeutic use; D005753:Gastric Mucosa / Q000098:blood supply / Q000473:pathology*; D006146:Guanidines / Q000494:pharmacology* / Q000627:therapeutic use; D006635:Histamine H2 Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D017665:Hydroxyl Radical; D008054:Lipid Peroxides / Q000097:blood / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D015427:Reperfusion Injury / Q000473:pathology; D013276:Stomach Ulcer / Q000473:pathology / Q000517:prevention & control*; D013450:Sulfones / Q000494:pharmacology* / Q000627:therapeutic use; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000897:Anti-Ulcer Agents; D016166:Free Radical Scavengers; D006146:Guanidines; D006635:Histamine H2 Antagonists; D008054:Lipid Peroxides; D013450:Sulfones; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; C088837:T 593; D017665:Hydroxyl Radical