Hepatic microsomal function in rats with chronic dietary iron overload.
Hepatic microsomal function in rats with chronic dietary iron overload.
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DOI：
10.1016/0016-5085(86)90251-9
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发表时间：
1986-06
期刊：
影响因子：
29.4
通讯作者：
B. Bacon;B. Bacon;J. Healey;J. Healey;G. Brittenham;G. Brittenham;C. H. Park;C. H. Park;J. Nunnari;J. Nunnari;A. Tavill;A. Tavill;H. Bonkovsky;H. Bonkovsky
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文献类型：
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作者：
B. Bacon;B. Bacon;J. Healey;J. Healey;G. Brittenham;G. Brittenham;C. H. Park;C. H. Park;J. Nunnari;J. Nunnari;A. Tavill;A. Tavill;H. Bonkovsky;H. Bonkovsky
我们确定了慢性膳食铁超负荷大鼠体内铁诱导的脂质过氧化反应是否与肝微粒体功能改变有关。在喂食2.0%羰基铁饲料20周的大鼠中，在平均（± SEM）肝铁浓度为1210 ± 92 μg/g肝脏（湿重）或2730 ± 100 μg/g时，未发现显著的微粒体共轭二烯形成（微粒体脂质过氧化的证据）或细胞色素P450浓度差异。然而，当肝脏铁浓度为4090 ± 245 μg/g时，共轭二烯形成显著（p < 0.001），细胞色素P450浓度降低56%（p < 0.001）。大鼠喂饲2.5%羰基铁饲料10周，肝铁浓度达4820 ± 420 μg/g，微粒体共轭二烯形成明显（p < 0.001），细胞色素P450减少35%（p < 0.005），氨基比林脱甲基酶活性降低16%（p < 0.025），但葡萄糖-6-磷酸酶活性仅降低8%（p =不显著）。最后，在喂食3.0%铁补充饮食7周的大鼠中，达到2730 ± 205 μg/g的肝脏铁浓度，细胞色素P450减少23（p < 0.025），细胞色素b5减少28%（p < 0.001），血红素加氧酶活性增加47%（p < 0.025）（血红素加氧酶活性仅在该组中测量）。我们的结论是，口服铁负荷可以产生微粒体脂质过氧化反应，在体内与微粒体血红素蛋白浓度和细胞色素P450依赖酶的选择性降低。
We determined whether alterations in hepatic microsomal function occur in association with ironinduced lipid peroxidation in vivo in rats with chronic dietary iron overload. In rats fed a 2.0% carbonyl iron diet for a period of 20 wk, there was no significant microsomal conjugated diene formation (evidence of microsomal lipid peroxidation) or difference in cytochrome P450concentration found at mean (± SEM) hepatic iron concentrations of 1210 ± 92 μg/g liver (wet wt) or 2730 ± 100 μg/g. At a hepatic iron concentration of 4090 ± 245 μg/g, however, there was significant conjugated diene formation (p < 0.001) and a 56% decrease in the cytochrome P450concentration (p < 0.001). In rats fed a 2.5% carbonyl iron diet for 10 wk, achieving a liver iron concentration of 4820 ± 420 μg/g, there was significant microsomal conjugated diene formation (p < 0.001), a 35% reduction in cytochrome P450(p < 0.005), and a 16% reduction in aminopyrine demethylase activity (p < 0.025), but only an 8% reduction in glucose-6-phosphatase activity (p = not significant). Finally, in rats fed a 3.0% iron-supplemented diet for 7 wk, achieving a liver iron concentration of 2730 ± 205 μg/g, there was a 23% reduction in cytochrome P450(p < 0.025), a 28% reduction in cytochrome b5(p < 0.001), and a 47% increase in heme oxygenase activity (p < 0.025) (heme oxygenase activity measured in this group only). We conclude that oral iron loading can produce microsomal lipid peroxidation in vivo that is associated with selective decreases in microsomal hemoprotein concentrations and cytochrome P450-dependent enzymes.