EBSELEN, A SELENOORGANIC 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 ethano l-induced murine gastric mucosal injury was examined. In an in vivo st udy, absolute ethanol (50 mu l/mouse, oral) produced marked gastric mu cosal necrosis along with hemorrhage or edema and elevations in both l ipid peroxide and peptidoleukotriene levels in the fundic mucosa. Pret reatment with ebselen (30 and 100 mg/kg, oral) significantly prevented this gastric mucosal injury and, further, remarkably decreased the el evated lipid peroxide and peptidoleukotriene levels. In an in vitro st udy using a murine gastric surface mucous cell line GSM06, exposure to ethanol concentration dependently elicited cell damage (7.5-17.5% eth anol) and an increase in lipid peroxides without alterations in peptid oleukotrienes (15% ethanol). Addition of ebselen (10 and 100 mu M) to this system (15% ethanol) significantly inhibited the cell damage and completely prevented the increase in lipid peroxide level. These resul ts indicate that ebselen protects against murine gastric mucosal injur y both in vivo and in vitro, and that this protection may be related a t least in part to its inhibitory action on lipid peroxides.