Lipid peroxidation in ethanol poisoning: a critical reconsideration.
Evidence for the existence of increased lipid peroxidation in the liver after ethanol administration to rats is discussed. A criticism of the methods used to measure lipid peroxidation is also given. Most authors who are in favour of the presence of lipid peroxidation after ethanol have used the detection of thiobarbituric acid (TBA)-reacting substances as a measure of lipid peroxidation. This test is not entirely satisfactory, because: (1) it is not specific; (2) it mostly measures malonaldehyde, a substance of low toxicity, following a 1-2 hr incubation time; (3) several aldehydes produced during lipid peroxidation do not react with TBA. However, it is now clear that the aldehydes produced during lipid peroxidation are actively metabolized by homogenates, so differences in catabolism may influence the result of a TBA test. Measurement of the diene conjugation band, the other test usually used to detect lipid peroxidation, produces information only on the presence of dienes at a given moment, but does not give any information on the production or decomposition rates of such dienes. Thus differences in production or decomposition kinetics may mask the results. Notwithstanding these criticisms, most of the evidence at present is in favour of some involvement of lipid peroxidation in ethanol intoxication. One hypothesis is that of the direct impact of ethanol-derived free radicals. Another is that ethanol provokes the formation of oxygen free radical species, which can start lipid peroxidation either directly, or by exhausting anti-oxidant substances in the cell so as to change the balance in favour of increased peroxidation. Finally, a third hypothesis is that acetaldehyde, the main product of ethanol oxidation, is able to stimulate lipid peroxidation, possibly through the formation of free radicals, or depletion of levels of antioxidant substances. Experiments consisting of measuring total glutathione (GSH and GSSG) during lipid peroxidation stimulated by ethanol or acetaldehyde show, however, that GSH is totally converted into GSSG during the incubation, thus suggesting that the antioxidant trapped by acetaldehyde is not GSH. In isolated hepatocytes, disulfiram, an inhibitor of aldehyde dehydrogenase, does not prevent the GSH decrease caused by acetaldehyde, but can block the induced lipid peroxidation. The relevance of increased lipid peroxidation to the mechanism of the liver damage induced by ethanol remains unclear.
D000079:Acetaldehyde / Q000378:metabolism; D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D000431:Ethanol / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005235:Fatty Liver, Alcoholic / Q000378:metabolism*; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D013858:Thiobarbiturates / Q000378:metabolism
D005230:Fatty Acids, Nonesterified; D005609:Free Radicals; D008054:Lipid Peroxides; D010743:Phospholipids; D013858:Thiobarbiturates; D009243:NAD; D000431:Ethanol; D008315:Malondialdehyde; D005978:Glutathione; D000079:Acetaldehyde; C029684:thiobarbituric acid