Polyenylphosphatidylcholine protects against alcohol but not iron-induced oxidative stress in the liver

Background: We reported before that, in baboons, the alcohol-induced oxidative stress in the liver is associated with depletion of dilinoleoylphosphatidylcholine [the major component of polyenylphosphatidylcholine (PPC)] and that both can be corrected by the administration of PPC, but we did not determine whether this protection extended to iron-induced oxidative stress. Methods: To compare the effects of PPC on alcohol- and iron-induced hepatic oxidative stress, 56 Sprague Dawley(R) male rats were pair-fed nutritionally adequate liquid diets containing ethanol (36% of energy) or isocaloric carbohydrate and PPC (3 mg/ml) or safflower oil (2.73 mg/ml), with or without 5 mg/ml carbonyl iron for 2 months. Markers of oxidative stress (4-hydroxynonenal and reduced glutathione), antioxidants (vitamin E, ubiquinol-9, and ubiquinol-10), and phosphatidylcholine (FC) species were assessed by HPLC and/or gas chromatography/mass spectrometry. Results: Alcohol feeding increased hepatic 4-hydroxynonenal 3-fold and decreased glutathione by 19%, ubiquinol-10 by 53%, and PC species containing arachidonate (palmitoyl- and stearoylarachidonoylphosphatidylcholines by 24% and 21%, respectively) and rotal phospholipids by 14%. PPC feeding prevented the rise of 4-hydroxynonenal, restored glutathione, and increased the hepatic content of dilinoleoylphosphatidylcholine and of some other PC carrying polyunsaturated fatty acids. Administration of iron alone increased hepatic iron, doubled 4-hydroxynonenal anti glutathione, whereas it decreased vitamin E, ubiquinol-9, total phospholipids, and several polyunsaturated PC. Alcohol given with iron further exacerbated the hepatic oxidative stress, as documented by the increase of 4-hydroxynonenal and the decrease in glutathione and ubiquinols-10. PPC did not prevent this oxidative stress, although it increased hepatic glutathione. Hepatic dilinoleoylphosphatidylcholine content was comparable with and without dietary iron. Conclusions: PPC prevents the alcohol-induced oxidative stress but only in the absence of iron overload.