HEPATIC LIPID-PEROXIDATION INVIVO IN RATS WITH CHRONIC IRON OVERLOAD
HEPATIC LIPID-PEROXIDATION INVIVO IN RATS WITH CHRONIC IRON OVERLOAD
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DOI：
10.1172/jci110787
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发表时间：
1983-01-01
影响因子：
15.9
通讯作者：
RECKNAGEL, RO
中科院分区：
文献类型：
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作者：
BACON, BR;TAVILL, AS;RECKNAGEL, RO
细胞膜脂质的过氧化分解是肝实质铁超载时肝细胞损伤的一种假定机制。在实验性慢性铁超载大鼠体内脂质过氧化的直接证据（如通过肝细胞器膜中脂质共轭二烯的形成来测量）进行了研究。两种胃肠外次氮基三乙酸铁（FeNTA）管理和饮食补充羰基铁被用来产生慢性铁超载。肝组织的生化和组织学评价证实了肝脏储存铁的中度增加。FeNTA管理产生过量的铁沉积在整个肝小叶的肝细胞和枯否细胞，而膳食羰基铁补充剂产生更大的肝铁超载门静脉周围分布与铁沉积主要在肝细胞。在实验性慢性Fe超负荷的两种模型中，在研究的所有3种平均肝Fe浓度（1197、3231和4216 μ g Fe/g）下证明了体内线粒体脂质过氧化的证据。相反，仅在通过膳食羰基Fe补充获得的较高肝Fe浓度（4161 μ g Fe/g）下，在微粒体脂质中检测到增加的共轭二烯形成。当在体外将Fe作为FeNTA或铁蛋白添加到正常肝匀浆中时，在脂质提取之前，没有观察到共轭二烯形成。共轭二烯的存在下，大鼠肝脏的亚细胞组分显然提供了直接的证据，铁诱导的肝线粒体和微粒体脂质过氧化反应在体内的2个模型的实验慢性铁过载。
Peroxidative decomposition of cellular membrane lipids is a postulated mechanism of hepatocellular injury in parenchymal Fe overload. Direct evidence of lipid peroxidation in vivo (as measured by lipid-conjugated diene formation in hepatic organelle membranes) was investigated in rats with experimental chronic Fe overload. Both parenteral ferric nitrilotriacetate (FeNTA) administration and dietary supplementation with carbonyl iron were used to produce chronic Fe overload. Biochemical and histologic evaluation of liver tissue confirmed moderate increases in hepatic storage Fe. FeNTA administration produced excessive Fe deposition throughout the hepatic lobule in both hepatocytes and Kupffer cells, whereas dietary carbonyl iron supplementation produced greater hepatic Fe overload in a periportal distribution with Fe deposition predominantly in hepatocytes. Evidence for mitochondrial lipid peroxidation in vivo was demonstrated at all 3 mean hepatic Fe concentrations studied (1197, 3231 and 4216 .mu.g Fe/g) in both models of experimental chronic Fe overload. In contrast, increased conjugated diene formation was detected in microsomal lipids only at the higher liver Fe concentration (4161 .mu.g Fe/g) achieved by dietary carbonyl Fe supplementation. When Fe as either FeNTA or ferritin was added in vitro to normal liver homogenates before lipid extraction, no conjugated diene formation was observed. The presence of conjugated dienes in the subcellular fractions of rat liver apparently provide direct evidence of Fe induced hepatic mitochondrial and microsomal lipid peroxidation in vivo in 2 models of experimental chronic Fe overload.