Ebselen, a seleno-organic compound, protects against ethanol-induced murine gastric mucosal injury in both in vivo and in vitro systems.
The inhibitory effect of the seleno-organic compound ebselen on ethanol-induced murine gastric mucosal injury was examined. In an in vivo study, absolute ethanol (50 microliters/mouse, oral) produced marked gastric mucosal necrosis along with hemorrhage or edema and elevations in both lipid peroxide and peptidoleukotriene levels in the fundic mucosa. Pretreatment with ebselen (30 and 100 mg/kg, oral) significantly prevented this gastric mucosal injury and, further, remarkably decreased the elevated lipid peroxide and peptidoleukotriene levels. In an in vitro study using a murine gastric surface mucous cell line GSM06, exposure to ethanol concentration dependently elicited cell damage (7.5-17.5% ethanol) and an increase in lipid peroxides without alterations in peptidoleukotrienes (15% ethanol). Addition of ebselen (10 and 100 microM) to this system (15% ethanol) significantly inhibited the cell damage and completely prevented the increase in lipid peroxide level. These results indicate that ebselen protects against murine gastric mucosal injury both in vivo and in vitro, and that this protection may be related at least in part to its inhibitory action on lipid peroxides.
Tabuchi
Y
Y
Exploratory Research Laboratories III, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Sugiyama
N
N
Horiuchi
T
T
Furusawa
M
M
Furuhama
K
K
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001393:Azoles / Q000097:blood / Q000494:pharmacology*; D002478:Cells, Cultured; D000431:Ethanol / Q000633:toxicity*; D005753:Gastric Mucosa / Q000187:drug effects*; D054833:Isoindoles; D015289:Leukotrienes / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016566:Organoselenium Compounds / Q000097:blood / Q000494:pharmacology*
D000897:Anti-Ulcer Agents; D001393:Azoles; D054833:Isoindoles; D015289:Leukotrienes; D008054:Lipid Peroxides; D016566:Organoselenium Compounds; D000431:Ethanol; C042986:ebselen