Aleynik S I, Leo M A, Aleynik M K, Lieber C S
Section of Liver Disease and Nutrition and Alcohol Research Center, Bronx VA Medical Center and Mount Sinai School of Medicine, New York, New York 10468, USA.
Alcohol Clin Exp Res. 2000 Feb;24(2):196-206.
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.
To compare the effects of PPC on alcohol- and iron-induced hepatic oxidative stress, 56 Sprague Dawley 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 (PC) species were assessed by HPLC and/or gas chromatography/mass spectrometry.
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 total 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 and 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.
PPC prevents the alcohol-induced oxidative stress but only in the absence of iron overload.
我们之前报道过,在狒狒中,肝脏中酒精诱导的氧化应激与二亚油酰磷脂酰胆碱(多烯磷脂酰胆碱的主要成分)的消耗有关,并且两者都可以通过给予多烯磷脂酰胆碱来纠正,但我们没有确定这种保护是否也适用于铁诱导的氧化应激。
为了比较多烯磷脂酰胆碱对酒精和铁诱导的肝脏氧化应激的影响,将56只雄性Sprague Dawley大鼠配对饲养,给予营养充足的液体饮食,其中含有乙醇(占能量的36%)或等热量的碳水化合物以及多烯磷脂酰胆碱(3毫克/毫升)或红花油(2.73毫克/毫升),同时添加或不添加5毫克/毫升羰基铁,持续2个月。通过高效液相色谱法和/或气相色谱/质谱法评估氧化应激标志物(4-羟基壬烯醛和还原型谷胱甘肽)、抗氧化剂(维生素E、泛醇-9和泛醇-10)以及磷脂酰胆碱种类。
喂食酒精使肝脏中4-羟基壬烯醛增加3倍,谷胱甘肽减少19%,泛醇-10减少53%,含有花生四烯酸的磷脂酰胆碱种类(棕榈酰和硬脂酰花生四烯酰磷脂酰胆碱分别减少24%和21%)以及总磷脂减少14%。喂食多烯磷脂酰胆碱可防止4-羟基壬烯醛升高,恢复谷胱甘肽水平,并增加肝脏中二亚油酰磷脂酰胆碱以及其他一些携带多不饱和脂肪酸的磷脂酰胆碱的含量。单独给予铁会增加肝脏铁含量,使4-羟基壬烯醛和谷胱甘肽增加一倍,而维生素E、泛醇-9、总磷脂以及几种多不饱和磷脂酰胆碱减少。与铁一起给予酒精会进一步加剧肝脏氧化应激,表现为4-羟基壬烯醛增加以及谷胱甘肽和泛醇-10减少。多烯磷脂酰胆碱虽然增加了肝脏谷胱甘肽,但并未预防这种氧化应激。无论有无膳食铁,肝脏中二亚油酰磷脂酰胆碱含量相当。
多烯磷脂酰胆碱可预防酒精诱导的氧化应激,但仅在无铁过载的情况下。