Demori Ilaria, Voci Adriana, Fugassa Emilia, Burlando Bruno
Dipartimento di Biologia, Università di Genova, Corso Europa 26, I-16132 Genova, Italy.
Alcohol. 2006 Nov;40(3):185-91. doi: 10.1016/j.alcohol.2006.12.006. Epub 2007 Mar 7.
Individuals affected by liver steatosis seldom have symptoms of liver injury, but may be particularly vulnerable to oxidative insults. In this study, we evaluated liver redox alterations produced by acute ethanol administration to rats that were fed a high-fat diet (HFD). Adult male Wistar rats were fed HFD or standard diet (controls) for 1 month; a group of animals from each condition were gavaged with 35% (vol/vol) ethanol every 12h for the last 3 days of the experiment. Total lipid content determined in liver showed lipid accumulation after HFD or HFD combined with ethanol. HFD alone induced a significant rise of seric alanine aminotransferase levels and a marked reduction of antioxidant enzyme activities (catalase, superoxide dismutase, glutathione transferase). Ethanol alone caused a significant rise of seric cholesterol levels and enhanced mitochondrial H2O2 production, but without apparent oxidative stress as evaluated by thiobarbituric acid-reactive substances (TBARS) assay. The combination of HFD and acute ethanol caused an increase of TBARS, indicating lipid peroxidation, most likely as a consequence of a decrease in antioxidant defenses induced by HFD and of an increase in reactive oxygen species production induced by ethanol. Principal component analysis, based on all the measured parameters, that is, serum liver function tests, antioxidant enzyme activities, mitochondrial H2O2 release, and TBARS, indicated that HFD and ethanol act as two independent factors. In conclusion, our results show that HFD or acute ethanol alone produce, at the most, mild liver injury, whereas their combination triggers oxidative stress, possibly inducing a progression toward liver disease. Hence, our data indicate that a diet too rich in fat is a serious risk factor for the occurrence of liver injury deriving from acute ethanol consumption.
患有肝脂肪变性的个体很少出现肝损伤症状，但可能特别容易受到氧化损伤。在本研究中，我们评估了给高脂饮食（HFD）喂养的大鼠急性给予乙醇后肝脏氧化还原的变化。成年雄性Wistar大鼠喂养HFD或标准饮食（对照）1个月；在实验的最后3天，每组动物每12小时灌胃35%（体积/体积）乙醇。肝脏中测定的总脂质含量显示，HFD或HFD与乙醇联合使用后出现脂质蓄积。单独的HFD导致血清丙氨酸转氨酶水平显著升高，抗氧化酶活性（过氧化氢酶、超氧化物歧化酶、谷胱甘肽转移酶）显著降低。单独的乙醇导致血清胆固醇水平显著升高，并增强线粒体过氧化氢的产生，但通过硫代巴比妥酸反应性物质（TBARS）测定评估，没有明显的氧化应激。HFD和急性乙醇的联合使用导致TBARS增加，表明脂质过氧化，这很可能是由于HFD诱导的抗氧化防御能力下降和乙醇诱导的活性氧产生增加所致。基于所有测量参数（即血清肝功能测试、抗氧化酶活性、线粒体过氧化氢释放和TBARS）的主成分分析表明，HFD和乙醇是两个独立的因素。总之，我们的结果表明，单独的HFD或急性乙醇最多只会产生轻度肝损伤，而它们的联合使用会引发氧化应激，可能导致向肝病的进展。因此，我们的数据表明，脂肪含量过高的饮食是急性乙醇摄入导致肝损伤发生的一个严重风险因素。
