Hepatic lipid peroxidation in hereditary hemochromatosis and alcoholic liver injury
Hepatic lipid peroxidation in hereditary hemochromatosis and alcoholic liver injury
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DOI：
10.1016/s0022-2143(99)90022-7
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发表时间：
1999-05-01
期刊：
影响因子：
--
通讯作者：
Bacon, B
中科院分区：
文献类型：
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作者：
Niemelä, O;Parkkila, S;Bacon, B
在实验动物中的研究表明，脂质过氧化增强可能在铁超载或过度饮酒引起的肝损伤中起作用，本研究的目的是比较遗传性血色沉着症(HH)患者和酒精滥用患者肝脏中脂质过氧化衍生醛的形成。对10例不饮酒的HH患者的肝活检标本进行了评价。根据肝铁指数或人类白细胞抗原与已知先证者的同一性，这些患者被分类为HH，所有患者都是Cys282Tyr突变纯合子。此外，还检查了8例酒精性肝病患者，其中2例还伴有血色素沉着，17例与铁负荷过高或酗酒无关的肝病患者作为对照。对肝活检标本进行丙二醛和4-羟基壬烯醛蛋白加合物免疫组织化学染色，发现HH和酗酒患者肝组织中丙二醛和4-羟基壬烯醛蛋白加合物的含量均高于对照组。在酒精中毒中，加合物主要在3区，而在血色沉着症中，腺泡1区染色占优势，这伴随着铁的定位。在酗酒和铁负荷过高的患者中，蛋白质加合物的含量最丰富。这些数据支持长期饮酒和铁超载都会导致肝脏脂质过氧化的观点。过量饮酒和铁超载可通过形成反应性醛类产物，对肝脏产生附加毒性作用。
Studies in experimental animals have indicated that enhanced lipid peroxidation may play a role in the hepatic injury produced by iron overload or by excessive alcohol consumption, The aim of this study was to compare the formation of lipid peroxidation-derived aldehydes in the liver of patients with hereditary hemochromatosis (HH) and alcohol abuse. Liver biopsy specimens from 10 nondrinking patients with HH were evaluated. These patients were classified as having HH based on hepatic iron index or human leukocyte antigen identity with a known proband, All patients were homozygous for the Cys282Tyr mutation. In addition, 8 patients with alcoholic liver disease were examined, 2 of whom also had hemochromatosis, For comparison, 17 patients with liver diseases unrelated to iron overload or alcohol abuse were studied. Liver biopsy specimens were immunostained for protein adducts with malondialdehyde and 4-hydroxynonenal, Both malondialdehyde- and 4-hydroxynonenal-protein adducts were found from liver specimens of patients with HH and alcohol abuse in more abundant amounts than from patients in a control group. In alcoholics the adducts were primarily in zone 3, whereas in hemochromatosis staining had an acinar zone 1 predominance, which followed the localization of iron. The most abundant amounts of protein adducts were noted in patients with alcohol abuse plus iron overload. The data support the concept that both chronic alcohol use and iron overload induce hepatic lipid peroxidation. Through formation of reactive aldehydic products, excessive alcohol consumption and iron overload may have additive hepatotoxic effects.