title: Chronic ethanol feeding increases 7-hydroperoxycholesterol and oxysterols in rat skeletal muscle.
abstract: It was our hypothesis that, as a consequence of increased oxidative stress, cholesterol-derived hydroperoxides and oxysterols are increased in skeletal muscles chronically exposed to ethanol. To test this we fed male Wistar rats (0.1 kg initial body weight) a nutritionally complete liquid diet containing ethanol as 35% of total calories: controls were pair-fed identical amounts of the same diet in which ethanol was replaced by isocaloric glucose. At the end of 1(1/2) months, soleus (type I fiber-predominant) and plantaris (type II fiber-predominant) skeletal muscles were dissected out. We measured 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). We identified and confirmed by LC-MS the presence of 7 alpha-OOH, 7 beta-OOH and 7 alpha-OH, 7 beta-OH and 7-keto in skeletal muscle of rats. We also showed that in response to chronic alcohol feeding, there were significant increases in soleus 7 alpha-OH (P =.0005), 7 beta-OH (P =.0005), and 7-keto (P =.0007). In the plantaris, mean 7 alpha-OH and 7-keto were not significantly altered (P >.05), but 7 beta-OH increased (P =.0418). This is the first report of 7 alpha-OH, 7 beta-OH, and 7-keto oxysterols being identified in skeletal muscle of rats. Their elevation in chronic experimental alcoholism, together with increases in cholesterol hydroperoxides, may possibly represent evidence of increased oxidative stress.
authors.affiliation: Department of Legal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Fujita
authors.forename: Junko
authors.initials: J
authors.lastname: Adachi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ueno
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Peters
authors.forename: Victor R
authors.initials: VR
authors.lastname: Preedy
mesh_terms: D000284:Administration, Oral; D000437:Alcoholism / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D002149:Energy Intake; D000431:Ethanol / Q000008:administration & dosage*; D005526:Food, Formulated; D006888:Hydroxycholesterols / Q000032:analysis / Q000378:metabolism*; D007653:Ketocholesterols / Q000032:analysis / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013995:Time
chemical_list: D006888:Hydroxycholesterols; D007653:Ketocholesterols; C041011:cholesterol 7-hydroperoxide; D000431:Ethanol; D002784:Cholesterol