Protective effect of ebselen, a seleno-organic compound, against the progression of acute gastric mucosal lesions induced by compound 48/80, a mast cell degranulator, in rats.
The protective effect of ebselen, which possesses glutathione peroxidase-like activity and antioxidative and anti-inflammatory properties, against the progression of acute gastric mucosal lesions was examined in rats with a single intraperitoneal injection of compound 48/80 (0.75 mg/kg). Ebselen (50, 100 or 200 mg/kg) was orally administered 0.5 h after compound 48/80 treatment, at which time gastric mucosal lesions appeared. Post-administered ebselen suppressed gastric mucosal lesion progression at 3 h after compound 48/80 treatment dose-dependently, although no dose of ebselen affected the decreased gastric mucosal blood flow and increased serum serotonin and histamine concentrations found at 3 h after the treatment. A decrease in Se-glutathione peroxidase activity and increases in myeloperoxidase and xanthine oxidase activities and the concentration of thiobarbituric acid reactive substances were found in gastric mucosal tissues at 0.5 h after compound 48/80 treatment, and these changes were further enhanced at 3 h. Post-administered ebselen attenuated all these changes found at 3 h after compound 48/80 treatment dose-dependently. The present results indicate that ebselen exerts a protective effect against the progression of compound 48/80-induced acute gastric mucosal lesions in rats, and they suggest that this protective effect of ebselen could be due to its glutathione peroxidase-like activity and its antioxidative and anti-inflammatory properties.
Ohta
Yoshiji
Y
Department of Chemistry, School of Medicine, Fujita Health University, Toyoake, Aichi, Japan. yohta@fujita-hu.ac.jp
Kobayashi
Takashi
T
Inui
Kazuo
K
Yoshino
Junji
J
Nakazawa
Saburo
S
D000208:Acute Disease; D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001393:Azoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects*; D006632:Histamine / Q000097:blood; D054833:Isoindoles; D008297:Male; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin / Q000097:blood; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D014969:Xanthine Oxidase / Q000378:metabolism; D003189:p-Methoxy-N-methylphenethylamine / Q000633:toxicity*
D000897:Anti-Ulcer Agents; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; D012701:Serotonin; D003189:p-Methoxy-N-methylphenethylamine; C042986:ebselen; D006632:Histamine; D009195:Peroxidase; D014969:Xanthine Oxidase