ESSENTIAL AMINO ACID SUPPLEMENTATION DECREASES LIVER DAMAGE INDUCED BY CHRONIC ETHANOL CONSUMPTION IN RATS
ESSENTIAL AMINO ACID SUPPLEMENTATION DECREASES LIVER DAMAGE INDUCED BY CHRONIC ETHANOL CONSUMPTION IN RATS
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DOI：
10.1177/039463201102400307
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发表时间：
2011-07-01
影响因子：
3.5
通讯作者：
Rezzani, R.
中科院分区：
文献类型：
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作者：
Corsetti, G.;Stacchiotti, A.;Rezzani, R.
滥用乙醇（EtOH）对肝脏的损害最大。EtOH及其代谢产物损害肝细胞代谢，导致细胞内蛋白质和脂质积累，增加自由基氧的产生。这些过程对线粒体呼吸链和线粒体DNA都是有毒的。我们最近的研究表明，在啮齿类动物的饮食中补充一种富含必需氨基酸的混合物（EAAem）可以显著增加心脏和骨骼肌的线粒体质量和数量，并改善老年动物的线粒体功能。因此，在本研究中，我们试图测试EAAem补充剂是否可以减少etoh引起的肝损伤。各组成年雄性Wistar大鼠分别饲喂标准日粮和随意饮水（对照组）、添加20% EtOH的饮水（EtOH组）或添加20% EtOH和EAAem （1.5 g/kg/d）的饮水（EtOH+EAAem组），为期2个月。测定各实验组动物肝脏中EtOH浓度，分析肝脏中脂肪（Oil-Red-O）、线粒体（Grp75、Cyt-c-ox）、内质网（Grp78）和炎症（血红素氧化酶1、iNOS和过氧化物酶体）标志物。饮用EAAem的大鼠通过限制脂肪变性、向静脉周围肝细胞募集更多线粒体和过氧化物酶体、刺激或恢复抗氧化标志物、限制炎症过程的表达和减少内质网应激，改善了EAAem诱导的肝脏结构变化。综上所述，这些结果表明，补充EAAem可能是预防和治疗etoh引起的肝损伤的一种有希望的策略。
The liver sustains the greatest damage from ethanol (EtOH) abuse. EtOH and its metabolites impair hepatocyte metabolism, causing intracellular accumulation of proteins and lipids and increasing radical oxygen species production. These processes are toxic to the mitochondrial respiratory chain and to mitochondrial DNA. We have recently shown that supplementating the diet of rodents with an essential amino acid-enriched mixture (EAAem) significantly increases mitochondrial mass and number in cardiac and skeletal muscles and improves mitochondrial function in aged animals. Thus, in this study we sought to test whether EAAem supplementation could reduce EtOH-induced liver damage. Groups of adult male Wistar rats were fed a standard diet and water ad libitum (the control group), drinking water with 20% EtOH (the EtOH group), or drinking water with 20% EtOH and EAAem supplementation (1.5 g/kg/day) (the EtOH+EAAem group) for 2 months. The blood EtOH concentration was measured, and markers for fat (Oil-Red-O), mitochondria (Grp75, Cyt-c-ox), endoplasmic reticulum (Grp78), and inflammation (Heme Oxigenase 1, iNOS, and peroxisomes) were analyzed in the liver of animals in the various experimental groups. EAAem supplementation in EtOH-drinking rats ameliorated EtOH-induced changes in liver structure by limiting steatosis, recruiting more mitochondria and peroxisomes mainly to perivenous hepatocytes, stimulating or restoring antioxidant markers, limiting the expression of inflammatory processes, and reducing ER stress. Taken together, these results suggest that EAAem supplementation may represent a promising strategy to prevent and treat EtOH-induced liver damage.