Polyenylphosphatidylcholine corrects the alcohol-induced hepatic oxidative stress by restoring S-adenosylmethionine
Polyenylphosphatidylcholine corrects the alcohol-induced hepatic oxidative stress by restoring S-adenosylmethionine
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DOI：
10.1093/alcalc/agg066
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发表时间：
2003-05-01
影响因子：
2.8
通讯作者：
Lieber, CS
中科院分区：
文献类型：
--
作者：
Aleynik, SI;Lieber, CS
目的：由于酒精性肝损伤的晚期与蛋氨酸腺苷转移酶（MAT）活性降低有关，我们想知道这是否已经发生在早期阶段，以及涉及的机制是什么。方法：将32只Sprague-Dawley大鼠在Lieber-DeCarli液体日粮中添加或不添加聚丙烯磷脂酰胆碱（PPC），并配对饲喂乙醇（36%能量）或等热量碳水化合物（对照组）。结果：2个月后，s -腺苷蛋氨酸（通过高效液相色谱测量）从68.2 +/- 5.1减少到36.2 +/- 3.4 nmol/g，与肝还原性谷胱甘肽（GSH）从4.95 +/- 0.20减少到4.09 +/- 0.08 mumol/g有关，4-羟基壬烯醛（4-HNE）从0.24 +/- 0.02增加到0.47 +/- 0.07 nmol/g，这是一种可靠的脂质过氧化标志物。肝脏s -腺苷蛋氨酸（SAMe）与GSH呈正相关（r = 0.5916），与4-HNE呈负相关（r = -0.6375）。饲喂PPC校正各组间所有数值和MAT活性无显著差异。结论：酒精喂养8周后，同样的消耗已经发生，并被PPC完全纠正，与PPC预防酒精诱导的氧化应激同时发生。由于磷脂酰胆碱（PCs）是通过SAMe对磷脂酰乙醇胺的甲基化在肝脏中产生的，因此PPC很可能通过提供PCs，减少SAMe的利用，从而有助于其恢复，补充谷胱甘肽并纠正酒精诱导的氧化应激。
Aims: Since the late stages of alcoholic liver injury are associated with decreased activity of methionine adenosyltransferase (MAT), we wondered whether this already occurs at the early stages and what is the mechanism involved. Methods: Sprague-Dawley rats (n = 32) were pair-fed ethanol (36% of energy) or isocaloric carbohydrates (control) in Lieber-DeCarli liquid diets, with or without polyenylphosphatidylcholine (PPC). Results: After 2 months, there was a striking depletion of S-adenosylmethionine (measured by high-performance liquid chromatography) from 68.2 +/- 5.1 to 36.2 +/- 3.4 nmol/g, associated with a reduction in hepatic reduced glutathione (GSH) from 4.95 +/- 0.20 to 4.09 +/- 0.08 mumol/g, and an increase from 0.24 +/- 0.02 to 0.47 +/- 0.07 nmol/g of 4-hydroxynonenal (4-HNE), a reliable marker of lipid peroxidation. Hepatic S-adenosylmethionine (SAMe) correlated positively with GSH (r = 0.5916) and negatively with 4-HNE (r = -0.6375). Feeding PPC corrected all values and MAT activity did not differ significantly between groups. Conclusions: SAMe depletion occurs already after 8 weeks of alcohol feeding and is fully corrected by PPC, in parallel with the prevention by PPC of the alcohol-induced oxidative stress. Since phosphatidylcholines (PCs) are produced in the liver via methylation of phosphatidylethanolamine by SAMe, it is likely that PPC, by providing PCs, decreases the utilization of SAMe and thereby contributes to its restoration, with replenishment of GSH and correction of the alcohol-induced oxidative stress.