Relationship between oxidative stress and antioxidant systems in the liver of patients with Wilson disease: Hepatic manifestation in Wilson disease as a consequence of augmented oxidative stress
Relationship between oxidative stress and antioxidant systems in the liver of patients with Wilson disease: Hepatic manifestation in Wilson disease as a consequence of augmented oxidative stress
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DOI：
10.1203/01.pdr.0000238341.12229.d3
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发表时间：
2006-10-01
影响因子：
3.6
通讯作者：
Tsukahara, Hirokazu
中科院分区：
文献类型：
--
作者：
Nagasaka, Hironori;Inoue, Ikuo;Tsukahara, Hirokazu
肝豆状核变性（WD）是一种以产生自由基的过量肝脏铜沉积为特征的遗传性疾病，氧化应激在肝病发病机制中的作用尚不清楚。本研究调查了氧化应激对肝脏的影响以及WD患者的肝脏抗氧化反应，使用的肝脏标本来自表现为轻度肝损伤（1组，n = 3）、中度或更严重肝损伤（11组，n = 5）、暴发性肝衰竭（111组，n = 5）和无症状携带者（n = 2）的患者。还原性谷胱甘肽（GSH）与氧化性谷胱甘肽（GSSG）的比值降低，硫代巴比妥酸反应物质（TBARS）（一种脂质过氧化产物）升高，在所有受影响的患者中，尤其是第11组和第III组患者。所有患者的mn依赖性超氧化物歧化酶（Mn-SOD）、cuzn依赖性超氧化物歧化酶（CuZn-SOD）和过氧化氢酶的活性和蛋白表达均下降，其中ⅲ组患者的活性和蛋白表达明显下降。仅III组患者谷胱甘肽过氧化物酶（GPx）活性降低。无任何临床表现的无症状携带者TBARS水平和GSH/GSSG比值正常，GSH和GSSG水平均升高。CuZn-SOD、MnSOD和过氧化氢酶活性均升高。这些结果表明，过量的铜衍生氧化剂有助于WD的肝脏疾病的发生和进展。
The role of oxidative stress in the pathogenesis of liver disease in Wilson disease (WD), a genetic disorder characterized by excess hepatic deposition of copper that generates free radicals, remains unclear. This study investigates oxidative stress on the liver and hepatic antioxidant responses in WD using liver specimens from affected patients showing mild liver damage (group 1, n = 3), moderate or greater liver damage (group 11, n = 5), and fulminant hepatic failure (group 111, n = 5) and from asymptomatic carriers (n = 2). Decreased ratios of reduced glutathione (GSH) to oxidized glutathione (GSSG) and increased thiobarbituric acid reactive substance (TBARS), a lipid peroxidation product, were found in every affected patient, especially in group 11 and III patients. Activities and protein expressions of Mn-dependent superoxide dismutase (Mn-SOD), CuZn-dependent superoxide dismutase (CuZn-SOD), and catalase were decreased in all patients, especially in group III patients. Glutathione peroxidase (GPx) activity was decreased only in group III patients. Asymptomatic carriers without any clinical manifestations showed normal TBARS level and GSH/GSSG ratio with increases in both GSH and GSSG levels. Their CuZn-SOD, MnSOD, and catalase activities were increased. These results suggest that excessive copper-derived oxidants contribute to development and progression of liver disease in WD.