EFFICIENT CLEARANCE OF NON-TRANSFERRIN-BOUND IRON BY RAT-LIVER - IMPLICATIONS FOR HEPATIC IRON LOADING IN IRON OVERLOAD STATES
EFFICIENT CLEARANCE OF NON-TRANSFERRIN-BOUND IRON BY RAT-LIVER - IMPLICATIONS FOR HEPATIC IRON LOADING IN IRON OVERLOAD STATES
复制标题
DOI：
10.1172/jci112125
复制
发表时间：
1985-01-01
影响因子：
15.9
通讯作者：
WEISIGER, RA
中科院分区：
文献类型：
--
作者：
BRISSOT, P;WRIGHT, TL;WEISIGER, RA
在血色素沉着症和其他与铁过载相关的疾病中，血浆中总铁的显著部分以不与转铁蛋白结合的低分子量复合物的形式循环。肝脏对这种形式的铁的有效和不受调节的清除可能是这些疾病的特征性肝铁负荷和毒性的原因。我们测试了这种可能性，通过检查代表性的铁复合物在单通灌注大鼠肝脏的肝脏去除过程。发现从超滤的人血清中对亚铁和三价铁55 Fe的肝摄取是高效的和有效不可逆的（1 μ M铁的单程提取，58-75%）。类似的高效率被视为铁络合特定的生理和非生理协调，包括组氨酸，柠檬酸盐，果糖，草酸盐和谷氨酸盐，和tricine，因为较低的血浆流速，单程提取这些铁络合物在体内应该更大。 放射自显影证实大部分铁已被实质细胞清除。从Krebs-tricine缓冲液中去除肝脏是饱和的，亚铁和三价铁具有相似的动力学参数（表观Km，14-22 μ M; Vmax，24-38 nmol min-1 g liver-1）。这些结果表明，血浆中高水平的非转铁蛋白结合铁可能是铁超载状态下肝脏铁负荷的重要原因。
In hemochromatosis and other disorders associated with iron overload, a significant fraction of the total iron in plasma circulates in the form of low molecular weight complexes not bound to transferrin. Efficient and unregulated clearance of this form of iron by the liver may account for the hepatic iron loading and toxicity that characterize these diseases. We tested this possibility by examining the hepatic removal process for representative iron complexes in the single-pass perfused rat liver. Hepatic uptake of both ferrous and ferric 55Fe from ultrafiltered human serum was found to be highly efficient and effectively irreversible (single-pass extraction of 1 .mu.M iron, 58-75%). Similar high efficiencies were seen for iron complexed to specific physiologic and nonphysiologic coordinators, including histidine, citrate, fructose, oxalate and glutamate, and tricine, Because of lower plasma flow rates, single-pass extraction of these iron complexes in vivo should be even greater. Autoradiography confirmed that most iron had been removed by parenchymal cells. Hepatic removal from Krebs-tricine buffer was saturable with similar kinetic parameters for ferrous and ferric iron (apparent Km, 14-22 .mu.M; Vmax, 24-38 nmol min-1 g liver-1). These findings suggest that high levels of non-transferrin-bound iron in plasma may be an important cause of hepatic iron loading in iron overload states.