Effect of chronic ethanol feeding on oxysterols in rat liver.
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.
Ariyoshi
Koichi
K
Department of Legal Medicine, Kobe University Graduate School of Medicine, SE5 9RS, 7 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Adachi
Junko
J
Asano
Migiwa
M
Ueno
Yasuhiro
Y
Rajendram
Rajkumar
R
Preedy
Victor R
VR
D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000302:isolation & purification; D004032:Diet; D000431:Ethanol / Q000633:toxicity*; D005947:Glucose / Q000494:pharmacology; D006888:Hydroxycholesterols / Q000302:isolation & purification / Q000378:metabolism*; D007653:Ketocholesterols / Q000302:isolation & purification / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D036401:Toxicity Tests, Chronic
D006888:Hydroxycholesterols; D007653:Ketocholesterols; D000431:Ethanol; C011724:cholest-5-en-3 beta,7 alpha-diol; C002843:cholesterol hydroperoxide; D002784:Cholesterol; D005947:Glucose; C003001:7-ketocholesterol