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 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.