Ebselen prevents early alcohol-induced liver injury in rats

Oxidants have been shown to be involved in alcohol-induced liver injury. Mo reover, 2-phenyl-1,2-benzisoselenazole-3(2H)-one (ebselen), an organoseleni um compound and glutathione peroxidase mimic, decreases oxidative stress an d protects against stroke clinically. This study was designed to test the h ypothesis that ebselen protects against early alcohol-induced liver injury in rats. Male Wistar rats were fed high-fat liquid diets with or without et hanol (10-16 g/kg/d) continuously for up to 4 weeks using the intragastric enteral feeding protocol developed by Tsukamoto and French. Ebselen (50 mg/ kg twice daily, intragastrically) or vehicle (1% tylose) was administered t hroughout the experiment. Mean urine ethanol concentrations were not signif icantly different between treatment groups, and ebselen did not affect body weight gains or cyclic patterns of ethanol concentrations in urine. After 4 weeks, serum ALT levels were increased significantly about 4-fold over co ntrol values (37 +/- 5 IU/I) by enteral ethanol (112 +/- 7 IU/l); ebselen b lunted this increase significantly (61 +/- 8 IU/I). Enteral ethanol also ca used severe fatty accumulation, mild inflammation, and necrosis in the live r (pathology score: 4.3 +/- 0.3). In contrast, these pathological changes w ere blunted significantly by ebselen (pathology score: 2.5 +/- 0.4). While there were no significant effects of either ethanol or ebselen on glutathio ne peroxidase activity in serum or liver tissue, ebselen blocked the increa se in serum nitrate/nitrite caused by ethanol. Furthermore, ethanol increas ed the activity of NF-KB over 5-fold, the number of infiltrating neutrophil s 4-fold, and the accumulation of 4-hydroxynonenal over 5-fold. Ebselen blu nted all of these effects significantly. These results indicate that ebsele n prevents early alcohol-induced liver injury, most likely by preventing ox idative stress, which decreases inflammation. (C) 2001 Elsevier Science Inc .