Cholesterol-derived hydroperoxides in alcoholic liver disease

Human liver samples from 33 patients were collected at autopsy (controls, n = 9; fatty liver, n = 12; liver cirrhosis, n = 12), and samples homogenize d. Lipids extracted with chloroform and methanol were injected into the oct yl column of a high-performance liquid chromatograph with post-column chemi luminescence. Liquid chromatography-mass spectrometry was developed to iden tify 7-hydroperoxycholest-5-en-3 beta-ol (7-OOH). We found that two cholest erol-derived hydroperoxides, 7 alpha-hydroperoxycholest-5-en-3 beta-ol (7 a lpha-OOH) and 7 beta-hydroperoxycholest-5-en-3 beta-ol (7 beta-OOH), are pr esent in significantly elevated amounts (12.4 and 25.0 nmol/g tissue, respe ctively) in lipid extracts from alcoholic fatty liver, but not in extracts from alcoholic cirrhotic liver. 7 alpha-OOH and 7 beta-OOH are early interm ediates produced during free radical-mediated cholesterol oxidation and can serve as molecular indicators of chain peroxidative damage in cell membran es. This is the first demonstration of 7 alpha-OOH and 7 beta-OOH accumulat ions in human liver, and it is presumed to reflect greater oxidative stress pathology in alcoholic fatty liver.