Dynamics of oxidative/nitrosative stress in mice with methionine-choline-deficient diet-induced nonalcoholic fatty liver disease
Dynamics of oxidative/nitrosative stress in mice with methionine-choline-deficient diet-induced nonalcoholic fatty liver disease
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DOI：
10.1177/0960327113506723
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发表时间：
2014-07-01
影响因子：
2.8
通讯作者：
Radosavljevic, T.
中科院分区：
文献类型：
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作者：
Jorgacevic, B.;Mladenovic, D.;Radosavljevic, T.
胰岛素抵抗、氧化应激和促炎细胞因子在非酒精性脂肪性肝病 (NAFLD) 的发病机制中发挥着关键作用。我们研究的目的是调查蛋氨酸胆碱缺乏（MCD）饮食诱导的小鼠 NAFLD 中氧化/亚硝化应激的动态。雄性C57BL/6小鼠分为以下各组： 第1组：标准饮食对照组；第 2 组：MCD 饮食 2、4 和 6 周（分别为 MCD2、MCD4 和 MCD6）。治疗后，采集肝脏和血液样本进行组织病理学、丙氨酸和天冬氨酸转氨酶、急性期反应物和氧化/亚硝化应激参数。与对照组相比，所有 MCD 喂养组的肝脏丙二醛水平均较高 (p < 0.01)，而亚硝酸盐 + 硝酸盐水平则呈逐渐增加。在所有 MCD 喂养组中，总超氧化物歧化酶及其同工酶的活性均显着降低 (p < 0.01)。尽管过氧化氢酶活性在所有时间间隔内 MCD 喂养的动物中均显着较低 (p < 0.01)，但该酶的活性在 MCD4 组中明显最低。与对照组相比，MCD4 (p < 0.05) 和 MCD6 组 (p < 0.01) 的肝脏谷胱甘肽含量较低。仅MCD6组的铁蛋白和C反应蛋白血清浓度显着较高。我们的研究表明，MCD 饮食会导致肝脏亚硝化应激逐渐升高。此外，肝脏抗氧化能力下降最明显的是在第四周，这意味着该时期最适合应用抗氧化剂，以预防非酒精性脂肪性肝炎，而不是最初的NAFLD阶段。
Insulin resistance, oxidative stress, and proinflammatory cytokines play a key role in pathogenesis of nonalcoholic fatty liver disease (NAFLD). The aim of our study was to investigate the dynamics of oxidative/nitrosative stress in methionine-choline-deficient (MCD) diet -induced NAFLD in mice. Male C57BL/6 mice were divided into following groups: group 1: control group on standard diet; group 2: MCD diet for 2, 4, and 6 weeks (MCD2, MCD4, and MCD6, respectively). After treatment, liver and blood samples were taken for histopathology, alanine-and aspartate aminotransferase, acute phase reactants, and oxidative/nitrosative stress parameters. Liver malondialdehyde level was higher in all MCD-fed groups versus control group (p < 0.01), while nitrites + nitrates level showed a progressive increase. The activity of total superoxide dismutase and its isoenzymes was significantly lower in all MCD-fed groups (p < 0.01). Although catalase activity was significantly lower in MCD-fed animals at all intervals (p < 0.01), the lowest activity of this enzyme was evident in MCD4 group. Liver content of glutathione was lower in MCD4 (p < 0.05) and MCD6 group (p < 0.01) versus control. Ferritin and C-reactive protein serum concentration were significantly higher only in MCD6 group. Our study suggests that MCD diet induces a progressive rise in nitrosative stress in the liver. Additionally, the most prominent decrease in liver antioxidative capacity is in the fourth week, which implies that application of antioxidants would be most suitable in this period, in order to prevent nonalcoholic steatohepatitis but not the initial NAFLD phase.