Division of Human Anatomy, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy.
Int J Immunopathol Pharmacol. 2011 Jul-Sep;24(3):611-9. doi: 10.1177/039463201102400307.
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 percent EtOH (the EtOH group), or drinking water with 20 percent 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.
肝脏承受着来自乙醇（EtOH）滥用的最大损害。EtOH 和其代谢产物损害肝细胞代谢，导致蛋白质和脂质在细胞内积累，并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 有毒。我们最近表明，用富含必需氨基酸的混合物（EAAem）补充啮齿动物的饮食，可显著增加心脏和骨骼肌中的线粒体质量和数量，并改善老年动物的线粒体功能。因此，在这项研究中，我们试图测试 EAAem 补充是否可以减少 EtOH 引起的肝损伤。成年雄性 Wistar 大鼠的几组被喂食标准饮食和自由饮水（对照组），饮用含 20%EtOH 的水（EtOH 组），或饮用含 20%EtOH 和 EAAem 补充剂（1.5 g/kg/天）的水（EtOH+EAAem 组），为期 2 个月。测量血液中的 EtOH 浓度，并分析动物肝脏中的脂肪标志物（油红-O）、线粒体标志物（Grp75、Cyt-c-ox）、内质网标志物（Grp78）和炎症标志物（血红素加氧酶 1、iNOS 和过氧化物酶体）。EAAem 补充剂可改善 EtOH 诱导的大鼠肝脏结构变化，限制脂肪变性，招募更多的线粒体和过氧化物酶体主要到肝窦周细胞，刺激或恢复抗氧化标志物，限制炎症过程的表达，减少内质网应激。综上所述，这些结果表明，EAAem 补充可能是预防和治疗 EtOH 引起的肝损伤的一种有前途的策略。
