It was our hypothesis that, as a consequence of increased oxidative stress,
cholesterol-derived hydroperoxides and
oxysterols are increased in livers of rats exposed to
ethanol. To test this we dosed Wistar rats (approximately 0.1 kg initial
body weight) with
ethanol chronically (rats fed a nutritionally complete liquid diet containing
ethanol as 35% of total calories; sampled liver at approximately 6-7 weeks). We measured concentrations of 7 alpha- and 7 beta-hydroperoxycholest-5-en-3 beta-ol (7 alpha-OOH and 7 beta-OOH) as well as 7 alpha- and
7 beta-hydroxycholesterol (7 alpha-
OH and 7 beta-
OH), and
3 beta-hydroxycholest-5-en-7-one (also termed 7-ketocholesterol; 7-keto). In response to chronic alcohol feeding, there were significant elevations in the concentrations of 7 alpha-OOH (+169%, P = 0.005) and 7 beta-OOH (+199%, P = 0.011). Increases in the concentrations of hepatic 7-keto (+74%, P = 0.01) and decreases in
cholesterol (-43%; P = 0.03) also occurred. In contrast, the concentrations of both 7 alpha-
OH and 7 beta-
OH were not significant (NS). However, when
oxysterols in chronic
ethanol-fed rats were expressed relative to
cholesterol there were significant increases in 7-keto/
cholesterol (P = 0.0006), 7 alpha-
OH/
cholesterol (P = 0.0018) and 7 beta-
OH/
cholesterol (P = 0.0047). In conclusion, this is the first report of increased 7 alpha-OOH, 7 beta-OOH, and 7-keto in liver of rats and their elevation in chronic experimental
alcoholism represent evidence of increased oxidative stress.