- 作者: Tomas Zima Lenka Fialova Oto Mestek Marta Jandebova Jirina Crkovska lvan Malbohan Stanislav Stipek Ludmila Mikulikova Petr Popov
- 作者服務機構: Institute of Clinical Chemistry, lst lnstitute of Medical Chemistry and Biochemistry and Department for Alcohol and Addiction, First Faculty of Medicine, Charles university, and Department of Analytical Chemistry, lnstitute of Chemical Technology, Prague, Czech Republic
- 中文摘要: --
- 英文摘要: Alcohol-induced oxidative stress is linked to the metabo-lism of ethanol. Three metabolic pathways of ethanolhave been described in the human body so far. Theyinvolve the following enzymes: alcohol dehydrogenase,microsomal ethanol oxidation system (MEOS) and cata-lase. Each of these pathways could produce free radicalswhich affect the antioxidant system. Ethanol per se,hyperlactacidemia and elevated NADH increase xan-thine oxidase activity, which results in the production ofsuperoxide.Lipid peroxidation and superoxide produc-tion correlate with the amount of cytochrome P450 2E1.MEOS aggravates the oxidative stress directly as well asindirectly by impairing the defense systems. Hydroxye-thyl radicals are probably involved in the alkylation ofhepatic proteins. Nitric oxide (NO) is one of the key fac-tors contributing to the vessel wall homeostasis, animportant mediator of the vascular tone and neuronaltransduction, and has cytotoxic effects. Stable metabo-lites-nitrites and nitrates-were increased in alcoholics(34.3 2.6 vs. 22.7 1.2 moI/I, p<0.001). High NOconcentration could be discussed for its excitotoxicityand may be linked to cytotoxicity in neurons, glia andmyelin. Formation of NO has been linked to an increasedpreference for and tolerance to alcohol in recent studies.Increased NO biosynthesis also via inducible NO syn-thase (NOS, chronic stimulation) may contribute to plate-let and endothelial dysfunctions. Comparison of chroni-cally ethanol-fed rats and controls demonstrates thatexposure to ethanol causes a decrease in NADPH dia-phorase activity (neuronal NOS) in neurons and fibers ofthe cerebellar cortex and superior colliculus (stratum gri-seum superficiale and intermedium) in rats. Thesechanges in the highly organized structure contribute tothe motor disturbances, which are associated with alco-hol abuse. Antiphospholipid antibodies (APA) in alco-holic patients seem to reflect membrane lesions, impair-ment of immunological reactivity, liver disease progres-sion,and they correlate significantly with the diseaseseverity. The low-density lipoprotein (LDL) oxidation issupposed to be one of the most important pathogenicmechanisms of atherogenesis, and antibodies againstoxidized LDL (oxLDL) are some kind of epiphenomenonof this process. We studied IgG oxLDL and four APA (an-ticardiolipin, anti phosphatidylserine, antiphosphatidyl-ethanolamine 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 washigher (71.6 4.1 vs. 44.2 2.7 pmoI/I,p<0.001). Theprevalence of studied APA in alcoholics with mildlyaffected liver function was higher than in controls, butnot significantly. On the contrary, changes of autoanti-bodies to IgG oxLDL revealed a wide range of IgG oxLDLtiters in a healthy population. These parameters do notappear to be very promising for the evaluation of the riskof atherosclerosis. Free radicals increase the oxidativemodification of LDL. This is one of the most importantmechanisms, which increases cardiovascular risk inchronic alcoholic patients.Important enzymatic antioxi-dant systems - superoxide dismutase and glutathioneperoxidase - are decreased in alcoholics. We did not findany changes of serum retinol and tocopherol concentra-tions in alcoholics, and blood and plasma selenium andcopper levels were unchanged as well. Only the zinc con-centration was decreased in plasma. It could be relatedto the impairment of the immune system in alcoholics.Measurement of these parameters in blood compart-ments does not seem to indicate a possible organ, e.g.liver deficiency.
- 中文關鍵字: --
- 英文關鍵字: Oxidative stress. Antioxidants. Ethanol. Alcoholism. Trace elements. Antiphospholipid antibodies. Oxidized low-density lipoprotein. Nitric oxide. Autoantibodies. Tocopherol. Retinol