Chronic ethanol feeding increases 7-hydroperoxycholesterol and oxysterols in rat skeletal muscle.

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. Copyright 2002, Elsevier Science (USA). All rights reserved.