Oxysterols and Alcoholic Liver Disease

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Abstract
A new theory is presented implicating oxidative cholesterol metabolism and oxysterols as possible factors in the development of alcoholic liver disease. Our present studies have revealed the accumulation of cholesta-3,5-dien-7-one, 13.05 .+-. 2.75 .mu.g/g (n = 8), and cholesta-4,6-dien-3-one, 2.26 .+-. 0.88 .mu.g/g (n = 8) in fatty alcoholic liver, as compared with controls, 0.21 .+-. 0.12 .mu.g/g (n = 7) and 0.3 .+-. 0.33 .mu.g/g (n = 7), respectively. Acetaldehyde at 1 to 6 micromolar concentration in the blood and tissues of alcoholics cannot account for the extent of tissue damage, nor can it adequately explain liver steatosis characterized by accumulation of cholesterol and fatty acids and their esters in the liver of alcoholics known for their poor dietary habits. Oxysterols may be the primary cause for the development of alcoholic liver diseases and damage to accessory tissues. Significantly lower levels of 7-ketocholesterol in fatty liver, 6.8 .+-. 3.5 .mu.g/g (n = 8), as compared with control, 36.85 .+-. 22.25 .mu.g/g (n = 7), may be responsible for the increased cholesterol content of the alcoholic liver due to the inhibitory properties of this sterol on HMG-CoA reductase in cholesterol biosynthesis.