Cholesterol‐derived hydroperoxides in alcoholic liver disease

Abstract

Human liver samples from 33 patients were collected at autopsy (controls’ n=9; fatty liver’ n=12; liver cirrhosis’ n=12)’ and samples homogenized. Lipids extracted with chloroform and methanol were injected into the octyl column of a high-performance liquid chromatograph with post-column chemiluminescence. Liquid chromatography-mass spectrometry was developed to identify 7-hydroperoxycholest-5-en-3β-ol (7-OOH). We found that two cholesterol-derived hydroperoxides’ 7α-hydroperoxycholest-5-en-3β-ol (7α-OOH) and 7β-hydroperoxycholest-5-en-3β-ol (7β-OOH)’ are present in significantly elevated amounts (12.4 and 25.0 nmol/g tissue’ respectively) in lipid extracts from alcoholic fatty liver’ but not in extracts from alcoholic cirrhotic liver. 7α-OOH and 7β-OOH are early intermediates produced during free radical-mediated cholesterol oxidation and can serve as molecular indicators of chain peroxidative damage in cell membranes. This is the first demonstration of 7α-OOH and 7β-OOH accumulations in human liver’ and it is presumed to reflect greater oxidative stress pathology in alcoholic fatty liver.