Alcohol-induced oxidative stress is linked to the metabolism of
ethanol. Three metabolic pathways of
ethanol have been described in the human body so far. They involve the following
enzymes:
alcohol dehydrogenase, microsomal
ethanol oxidation system (
MEOS) and
catalase. Each of these pathways could produce
free radicals which affect the
antioxidant system.
Ethanol per se, hyperlactacidemia and elevated
NADH increase
xanthine oxidase activity, which results in the production of
superoxide. Lipid peroxidation and
superoxide production correlate with the amount of
cytochrome P450 2E1.
MEOS aggravates the oxidative stress directly as well as indirectly by impairing the defense systems. Hydroxyethyl radicals are probably involved in the alkylation of hepatic
proteins.
Nitric oxide (NO) is one of the key factors contributing to the vessel wall homeostasis, an important mediator of the vascular tone and neuronal transduction, and has cytotoxic effects. Stable metabolites--
nitrites and
nitrates--were increased in alcoholics (34.3 +/- 2.6 vs. 22.7 +/- 1.2 micromol/l, p < 0.001). High NO concentration could be discussed for its excitotoxicity and may be linked to cytotoxicity in neurons, glia and myelin. Formation of NO has been linked to an increased preference for and tolerance to alcohol in recent studies. Increased NO biosynthesis also via inducible
NO synthase (NOS, chronic stimulation) may contribute to platelet and endothelial dysfunctions. Comparison of chronically
ethanol-fed rats and controls demonstrates that exposure to
ethanol causes a decrease in
NADPH diaphorase activity (neuronal NOS) in neurons and fibers of the cerebellar cortex and superior colliculus (stratum griseum superficiale and intermedium) in rats. These changes in the highly organized structure contribute to the motor disturbances, which are associated with
alcohol abuse.
Antiphospholipid antibodies (APA) in alcoholic patients seem to reflect membrane lesions, impairment of immunological reactivity,
liver disease progression, and they correlate significantly with the disease severity. The
low-density lipoprotein (
LDL) oxidation is supposed to be one of the most important pathogenic mechanisms of
atherogenesis, and
antibodies against
oxidized LDL (
oxLDL) are some kind of epiphenomenon of this process. We studied
IgG oxLDL and four APA (anticardiolipin, antiphosphatidylserine, antiphosphatidylethanolamine and antiphosphatidylcholine
antibodies). The
IgG oxLDL (406.4 +/- 52.5 vs. 499.9 +/- 52.5 mU/ml) was not affected in alcoholic patients, but
oxLDL was higher (71.6 +/- 4.1 vs. 44.2 +/- 2.7 micromol/l, p < 0.001). The prevalence of studied APA in alcoholics with mildly affected liver function was higher than in controls, but not significantly. On the contrary, changes of
autoantibodies to
IgG oxLDL revealed a wide range of
IgG oxLDL titers in a healthy population. These parameters do not appear to be very promising for the evaluation of the risk of
atherosclerosis.
Free radicals increase the oxidative modification of
LDL. This is one of the most important mechanisms, which increases cardiovascular risk in chronic alcoholic patients. Important enzymatic
antioxidant systems -
superoxide dismutase and
glutathione peroxidase - are decreased in alcoholics. We did not find any changes of serum
retinol and
tocopherol concentrations in alcoholics, and blood and plasma
selenium and
copper levels were unchanged as well. Only the
zinc concentration was decreased in plasma. It could be related to the impairment of the immune system in alcoholics. Measurement of these parameters in blood compartments does not seem to indicate a possible organ, e.g. liver deficiency.