The effects of moderate ethanol consumption on the liver of the monkey, Macaca fascicularis
The effects of moderate ethanol consumption on the liver of the monkey, Macaca fascicularis
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DOI：
10.1097/01.alc.0000095633.26284.fa
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发表时间：
2003-11-01
影响因子：
3.2
通讯作者：
Cunningham, C
中科院分区：
文献类型：
--
作者：
Ivester, P;Shively, CA;Cunningham, C
背景资料：虽然已经积累了适量饮酒对心脏保护作用的证据，但人们对每天饮酒两杯对肝脏的影响知之甚少。本研究的目的是确定适度的乙醇管理的影响对肝脏的酶的含量参与乙醇氧化，对肝脏脂质积累，并对血清标志物的肝功能/损伤的猴子，Macacafascicularis.Methods：卵巢切除，成年猴维持34个月的致动脉粥样硬化的饮食含有胆固醇1.21毫克/千焦。训练他们以0.5 g/kg体重的剂量饮用乙醇加溶媒，每周给药5天，持续2年。收集血液用于乙醇浓度（乙醇给药后1小时），并测定γ-谷氨酰转移酶、丙氨酸氨基转移酶（ALT）和碱性磷酸酶（ALP）活性。在尸检时获得的肝脏进行了分析，甘油三酯和胆固醇含量和乙醇脱氢酶，细胞色素P450 2 E1，细胞色素P450 3A 4通过Western blott.Results：乙醇给药后1小时测得的血液乙醇浓度相对恒定超过2年的给药期。消耗乙醇的动物和对照动物的肝脏乙醇脱氢酶和细胞色素P450水平没有显着差异。由于对照组和乙醇消费者肝脏脂质含量的高度变异性，乙醇相关的肝脏甘油三酯增加并不显著。然而，使用血浆胆固醇和载脂蛋白A-I的预处理浓度的协方差分析表明，肝脏游离胆固醇的乙醇相关增加是显着的。相对于对照组，酒精消费者有较高水平的血清ALT和ALP在5 months.Conclusions：在这项研究中对灵长类动物给动脉粥样硬化饮食的观察表明，适度的乙醇摄入对肝脏有适度的影响，包括轻微增加ALT和ALP值。然而，需要进行更多的研究来验证这种消费水平在长时间摄入时是否具有肝毒性。这仍然是一个问题，因为一些人类研究表明，被认为是心脏保护的乙醇水平在一生中消耗时会导致肝损伤。
Background: Although evidence has accumulated for the cardioprotective effects of moderate ethanol consumption, little is known about the effects on the liver of consuming the equivalent of two drinks per day. The objective of this study was to determine the effects of moderate ethanol administration on the hepatic content of enzymes involved in ethanol oxidation, on hepatic lipid accumulation, and on serum markers of liver function/damage in the monkey, Macaca fascicularis.Methods: Ovariectomized, adult monkeys were maintained for 34 months on an atherogenic diet containing cholesterol 1.21 mg/kJ. They were trained to drink ethanol plus vehicle at a dose of 0.5 g/kg body weight, which was administered 5 days a week for 2 years. Blood was collected for ethanol concentrations (1 hr after ethanol administration) and was also assayed for gamma-glutamyltransferase, alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities. Liver obtained at necropsy was analyzed for triglyceride and cholesterol contents and for alcohol dehydrogenase, cytochrome P450 2E1, and cytochrome P450 3A4 by Western blots.Results: The blood ethanol concentrations measured 1 hr after ethanol administration were relatively constant over the 2-year dosing period. Hepatic levels of alcohol dehydrogenase and the cytochrome P450s were not significantly different between ethanol-consuming animals and control animals. Ethanol-associated increases in liver triglyceride were not significant due to high variability in hepatic lipid content in both the controls and ethanol consumers. However, covariance analyses using pretreatment concentrations of plasma cholesterol and apolipoprotein A-I suggested that the ethanol-related increase in hepatic free cholesterol was significant. Relative to controls, alcohol consumers had higher levels of serum ALT and a transient increase in ALP at 5 months.Conclusions: The observations made in this study on primates administered an atherogenic diet suggest that moderate ethanol ingestion has modest effects on the liver, including slightly increased ALT and ALP values. However, additional studies will be required to verify that this level of consumption is hepatotoxic when ingested over extended periods. This is still a concern because some human studies suggest that levels of ethanol considered to be cardioprotective cause liver injury when consumed over a lifetime.