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铁和次氮基三乙酸(NTA)在大鼠肝脏中的摄取以及铁-次氮基三乙酸的毒性作用。

Uptake of iron and nitrilotriacetate (NTA) in rat liver and the toxic effect of Fe-NTA.

作者信息

Matsuura R

出版信息

Acta Med Okayama. 1983 Oct;37(5):393-400. doi: 10.18926/AMO/32422.

DOI:10.18926/AMO/32422
PMID:6316757
Abstract

A previous study has shown that a single injection of ferric nitrilotriacetate (Fe-NTA) produces hepatic parenchymal iron loading in rats. The present paper reports on iron uptake by rat liver and iron toxicity in the liver after a single injection of Fe-NTA (7.5 mg Fe/kg B.W.). Iron uptake was examined with 59Fe-NTA and Fe-[14C]-NTA. Thirty percent of the injected 59Fe was incorporated in the liver non-heme iron fraction at 3 h and retained for 240 h. Only 1% of the 14C injected as Fe-[14C]-NTA was taken up by the liver at 3 h. Gel filtration with a Sephadex G-25 column of the supernatant fraction of the liver obtained 3 h after the injection showed two peaks of 14C activity. One was eluted in the void volume, and the other corresponded to [14C]-NTA. The former had a molecular weight of 5,000-10,000 as determined with a Sephacryl S-300 column and also had 59Fe activity. The electron spin resonance spectra showed that the generation of a free radical in the liver was initiated within 1 h of the iron administration. The free radical generated in the serum by Fe-NTA was revealed to be superoxide by the spin trapping method. These results suggest that Fe-NTA transfers iron to transferrin in the serum and induces hepatic iron loading. Small amounts of the injected iron were taken up by the liver as Fe-NTA and generated superoxide which may have induced lipid peroxidation of the cellular membranes.

摘要

先前的一项研究表明,单次注射次氮基三乙酸铁(Fe-NTA)会使大鼠肝实质铁负荷增加。本文报道了单次注射Fe-NTA(7.5毫克铁/千克体重)后大鼠肝脏对铁的摄取及肝脏中的铁毒性。用59Fe-NTA和Fe-[14C]-NTA检测铁摄取情况。注射的59Fe中有30%在3小时时被肝脏非血红素铁组分摄取并保留240小时。作为Fe-[14C]-NTA注射的14C在3小时时只有1%被肝脏摄取。对注射后3小时获得的肝脏上清液组分用Sephadex G-25柱进行凝胶过滤,显示出两个14C活性峰。一个在空体积处洗脱,另一个对应于[14C]-NTA。用Sephacryl S-300柱测定,前者的分子量为5000 - 10000,并且也有59Fe活性。电子自旋共振光谱表明,在给予铁后1小时内肝脏中就开始产生自由基。通过自旋捕获法发现,Fe-NTA在血清中产生的自由基是超氧化物。这些结果表明,Fe-NTA将铁转移到血清中的转铁蛋白上并诱导肝脏铁负荷增加。少量注射的铁以Fe-NTA的形式被肝脏摄取并产生超氧化物,超氧化物可能诱导了细胞膜的脂质过氧化。

相似文献

1
Uptake of iron and nitrilotriacetate (NTA) in rat liver and the toxic effect of Fe-NTA.铁和次氮基三乙酸(NTA)在大鼠肝脏中的摄取以及铁-次氮基三乙酸的毒性作用。
Acta Med Okayama. 1983 Oct;37(5):393-400. doi: 10.18926/AMO/32422.
2
[Pathogenesis and mechanism of iron overload: ferric nitrilotriacetate, hemosiderin, active oxygen, and carcinogenesis].铁过载的发病机制:次氮基三乙酸铁、含铁血黄素、活性氧与致癌作用
Rinsho Ketsueki. 1989 Aug;30(8):1115-27.
3
Lipid peroxidation stimulated by iron nitrilotriacetate in rat liver.次氮基三乙酸铁刺激大鼠肝脏中的脂质过氧化反应。
Biochem Pharmacol. 1986 Jul 15;35(14):2381-7. doi: 10.1016/0006-2952(86)90465-x.
4
Kinetic evaluation of free malondialdehyde and enzyme leakage as indices of iron damage in rat hepatocyte cultures. Involvement of free radicals.
Biochem Pharmacol. 1990 Jun 1;39(11):1647-55. doi: 10.1016/0006-2952(90)90107-v.
5
Radical-promoting "free" iron level in the serum of rats treated with ferric nitrilotriacetate: comparison with other iron chelate complexes.用次氮基三乙酸铁处理的大鼠血清中促进自由基产生的“游离”铁水平:与其他铁螯合物的比较。
Acta Med Okayama. 1991 Dec;45(6):401-8. doi: 10.18926/AMO/32180.
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Modulation by iron loading and chelation of the uptake of non-transferrin-bound iron by human liver cells.铁负载和螯合对人肝细胞摄取非转铁蛋白结合铁的调节作用。
Biochim Biophys Acta. 1995 Apr 13;1243(3):373-80. doi: 10.1016/0304-4165(94)00162-q.
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Generation of active oxygen species by iron nitrilotriacetate (Fe-NTA).
Acta Med Okayama. 1986 Jun;40(3):163-73. doi: 10.18926/AMO/31938.
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Role of superoxide radicals in cytotoxic effects of Fe-NTA on cultured normal liver epithelial cells.超氧自由基在Fe-NTA对培养的正常肝上皮细胞细胞毒性作用中的作用。
Cell Struct Funct. 1987 Oct;12(5):407-20. doi: 10.1247/csf.12.407.
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Thiobarbituric acid-reactive substance formation of rat kidney brush border membrane vesicles induced by ferric nitrilotriacetate.次氮基三乙酸铁诱导大鼠肾刷状缘膜囊泡的硫代巴比妥酸反应性物质形成。
Arch Biochem Biophys. 1989 Nov 1;274(2):348-54. doi: 10.1016/0003-9861(89)90448-7.
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Protective effect of Rumex patientia (English Spinach) roots on ferric nitrilotriacetate (Fe-NTA) induced hepatic oxidative stress and tumor promotion response.皱叶酸模(洋菠菜)根对次氮基三乙酸铁(Fe-NTA)诱导的肝脏氧化应激和肿瘤促进反应的保护作用。
Food Chem Toxicol. 2007 Oct;45(10):1821-9. doi: 10.1016/j.fct.2007.03.021. Epub 2007 Apr 19.

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