Alcohol-induced generation of lipid peroxidation products in humans

To address the hypothesis that elevated blood alcohol increases systemic ox idant stress, we measured urinary excretion of isoprostanes (iPs), free rad ical-catalyzed products of arachidonic acid. Ten healthy volunteers receive d acute doses of alcohol (Everclear-R) or placebo under randomized, control led, double-blind conditions. Urinary iPF2a-III increased in a time- and do sage-dependent manner after dosing with alcohol, with the peak urinary iPF2 a-III excretion correlating with the rise in blood alcohol. To determine wh ether oxidant stress was associated with alcohol-induced liver disease (ALD ), we then studied the excretion of iPs in individuals with a documented hi story of alcohol-induced hepatitis or alcohol-induced chronic liver disease (AC). Both urinary iPF2a-III and urinary iPF2a-VI were markedly increased in patients with acute alcoholic hepatitis. In general, urinary iPF2a-III w as significantly elevated in cirrhotic patients, relative to controls, but its excretion was more pronounced when cirrhosis was induced by alcohol tha n by hepatitis C. Excretion of iPF2a-VI, as well as 4-hydroxynonenal and th e iPF2a-III metabolite, 2,3-dinor-5,6-dihydro-iPF2a-III, was also increased in AC. Vitamin C, but not aspirin, reduced urinary iPs in AC. Thus, vasoac tive iPs, which serve as indices of oxidant stress, are elevated in the uri ne in both acute and chronic ALD. Increased generation of iPs by alcohol in healthy volunteers is consistent with the hypothesis that oxidant stress p recedes and contributes to the evolution of ALD.