Preventive effect of ebselen on acute gastric mucosal lesion development in rats treated with compound 48/80.
The preventive effect of ebselen, a seleno-organic compound, which is known to possess glutathione peroxidase-like activity and antioxidative and anti-inflammatory properties, on the development of acute gastric mucosal lesions was examined in rats with a single injection of compound 48/80 (0.75 mg/kg, i.p.), a mast cell degranulator. Pre-administration of ebselen (p.o.) at a dose of 50 or 100 mg/kg, but not 10 mg/kg, prevented gastric mucosal lesion development at 3 h, but not gastric mucosal lesion formation at 0.5 h, after compound 48/80 injection, although any dose of pre-administered ebselen did not affect decreased gastric mucosal blood flow and increased serum serotonin and histamine concentrations found at 0.5 and 3 h after compound 48/80 injection. A decrease in Se-glutathione peroxidase activity and increases in the activities of myeloperoxidase, an index of tissue neutrophil infiltration, and xanthine oxidase and the concentration of thiobarbituric acid reactive substances, an index of lipid peroxidation, were found in gastric mucosal tissues at 0.5 h after compound 48/80 injection and these changes were further enhanced at 3 h. Pre-administration of ebselen (p.o.) at a dose of 50 or 100 mg/kg, but not 10 mg/kg, attenuated all these changes found at 3 h after compound 48/80 injection. These preventive effects of ebselen occurred in a dose-dependent manner. The present results indicate that pre-administered ebselen prevents the development of compound 48/80-induced acute gastric mucosal lesions in rats, and suggest that this preventive effect of ebselen could be due to its glutathione peroxidase-like activity and antioxidative and anti-inflammatory properties.
Department of Internal Medicine, Second Teaching Hospital, School of Medicine, Fujita Health University, Otobashi, Nakagawa-ku, Aichi 454-0012, Nagoya, Japan.
T
T
Kobayashi
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Y
Ohta
J
J
Yoshino
D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage*; D001393:Azoles / Q000008:administration & dosage*; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects*; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D006632:Histamine / Q000097:blood; D054833:Isoindoles; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D016566:Organoselenium Compounds / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000097:blood; D013276:Stomach Ulcer / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014969:Xanthine Oxidase / Q000187:drug effects / Q000378:metabolism; D003189:p-Methoxy-N-methylphenethylamine
D000897:Anti-Ulcer Agents; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; D017392:Thiobarbituric Acid Reactive Substances; D012701:Serotonin; D003189:p-Methoxy-N-methylphenethylamine; C042986:ebselen; D006632:Histamine; D005979:Glutathione Peroxidase; D014969:Xanthine Oxidase