Effect of gefarnate on acute gastric mucosal lesion progression in rats treated with compound 48/80, a mast cell degranulator, in comparison with that of teprenone.
We have reported that teprenone (geranylgeranylacetone), an anti-ulcer drug, prevents acute gastric mucosal lesion progression in rats treated once with compound 48/80 (C48/80), a mast cell degranulator, possibly by suppressing mucus depletion, neutrophil infiltration, and oxidative stress in the gastric mucosa. Herein, we examined the preventive effect of gefarnate (geranyl farnesylacetate), an anti-ulcer drug, on acute gastric mucosal lesion progression in rats treated once with C48/80 (0.75 mg/kg, i.p.) in comparison with that of teprenone, because the chemical structure and anti-ulcer action of gefarnate are similar to those of teprenone. Gefarnate (50, 100 or 200 mg/kg) administered orally at 0.5 h after C48/80 treatment, at which time gastric mucosal lesions appeared, reduced progressive gastric mucosal lesions at 3 h dose-dependently. At 3 h after C48/80 treatment, the gastric mucosa had decreased adherent mucus and hexosamine contents and increased myeloperoxdiase (an index of neutrophil infiltration) and xanthine oxidase activities and thiobarbituric acid reactive substances (an index of lipid peroxidation) content. Post-administered gefarnate attenuated all these changes dose-dependently. These preventive effects of gefarnate were similar to those of teprenone at a dose of 200 mg/kg. Post-administered gefarnate did not affect the increases in serum serotonin and histamine concentrations and the decrease in gastric mucosal blood flow at 3 h after C48/80 treatment like teprenone. These results indicate that orally administered gefarnate prevents acute gastric mucosal lesion progression in C48/80-treated rats possibly by suppressing mucus depletion, neutrophil infiltration, and oxidative stress in the gastric mucosa like teprenone.
Ohta
Yoshiji
Y
Department of Chemistry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan. yohta@fujita-hu.ac.jp
Kobayashi
Takashi
T
Imai
Yoichiro
Y
Inui
Kazuo
K
Yoshino
Junji
J
Nakazawa
Saburo
S
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D015550:Cell Degranulation / Q000187:drug effects*; D004224:Diterpenes / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D005778:Gefarnate / Q000494:pharmacology*; D006595:Hexosamines / Q000378:metabolism; D006632:Histamine / Q000097:blood; D008297:Male; D008407:Mast Cells / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism; D003189:p-Methoxy-N-methylphenethylamine / Q000633:toxicity*
D000897:Anti-Ulcer Agents; D004224:Diterpenes; D006595:Hexosamines; D017392:Thiobarbituric Acid Reactive Substances; D005778:Gefarnate; D012701:Serotonin; D003189:p-Methoxy-N-methylphenethylamine; D006632:Histamine; D009195:Peroxidase; D014969:Xanthine Oxidase; C031049:geranylgeranylacetone