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-3 beta-ol (7-OOH). We found that two cholesterol-derived hydroperoxides, 7 alpha-hydroperoxycholest-5-en-3 beta-ol (7 alpha-OOH) and 7 beta-hydroperoxycholest-5-en-3 beta-ol (7 beta-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. 7 alpha-OOH and 7 beta-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 7 alpha-OOH and 7 beta-OOH accumulations in human liver, and it is presumed to reflect greater oxidative stress pathology in alcoholic fatty liver.
Department of Legal Medicine, Kobe University School of Medicine, Japan.
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M
Asano
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Adachi
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Ueno
D000328:Adult; D002784:Cholesterol / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005235:Fatty Liver, Alcoholic / Q000378:metabolism*; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism*; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism*; D008163:Luminescent Measurements; D008875:Middle Aged
D008054:Lipid Peroxides; D002784:Cholesterol