Desferri-Exochelin, a lipid-soluble, hexadentate iron chelator, effectively removes tissue iron.
Desferri-Exochelin, a lipid-soluble, hexadentate iron chelator, effectively removes tissue iron.
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Desferri-Exochelin 是一种脂溶性六齿铁螯合剂，可有效去除组织铁。
DOI：
10.1016/j.trsl.2006.03.003
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Horwitz,LawrenceD
中科院分区：
文献类型：
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作者：
Hodges,YvonneK;Weinberger,HowardD;Stephens,Janet;Horwitz,MarcusA;Horwitz,LawrenceD
慢性铁超载会损害心脏、肝脏和其他器官。需要更好的铁络合剂来治疗这种严重的疾病。本文研究了脂溶性六齿铁螯合剂Desferri-Exochelin 772SM(D-Exo)在啮齿动物体内的摄取和分布，并评价了其对组织中铁的去除效果。给大鼠静脉注射氚D-Exo后，计数迅速从血液中消失，并在15个被研究的器官中迅速出现，通常在15分钟内达到峰值。心脏和肝脏有相当大的摄取，这两个器官特别容易受到临床铁负荷的损害。为了评估D-Exo对心脏和肝脏铁的实际降低作用，研究了42毫克右旋糖苷铁(2100 mg/kg)负荷的小鼠。与未加铁处理的对照组相比，9周后处死的铁负荷小鼠的心脏铁含量增加了4倍，肝脏铁含量增加了20倍。在铁负荷的小鼠中，用7 mg的D-Exo，每周4天，连续8周(总共224 mg)，用原子吸收法测量，肝脏和心脏的组织铁分别减少了20%和25%(P<；每个器官0.01)。在D-Exo剂量后的前8小时内，铁从尿液中排出。接受D-Exo治疗的小鼠体重正常增加，没有显示出毒性的证据。总之，在这个铁负荷过高的小鼠模型中，D-Exo静脉注射或ip。迅速扩散到多个器官，包括心脏和肝脏，并有效地清除铁而没有明显的毒性。
Chronic iron-overload is damaging to the heart, liver, and other organs. Better iron chelators are needed to treat this serious medical condition. The uptake and distribution of the lipid-soluble, hexadentate iron chelator desferri-Exochelin 772SM (D-Exo) is studied and its efficacy in removing iron from tissue in rodent models is evaluated. After an intravenous bolus of tritiated D-Exo to rats, counts rapidly disappeared from the blood and rapidly appeared in 15 organs studied, usually peaking within 15 min. There was considerable uptake in the heart and liver, 2 organs especially susceptible to damage from clinical iron overload. To assess actual decreases in cardiac and hepatic iron in response to D-Exo, mice loaded with 42 mg of iron dextran (2100 mg/kg) were studied. Untreated, iron-loaded mice sacrificed 9 weeks later had a 4-fold increase in cardiac iron and a 20-fold increase in hepatic iron compared with controls that were not iron-loaded. In iron-loaded mice treated with 7 mg of D-Exo intraperitoneally (i.p.) 4 days/week for 8 weeks (total 224 mg), tissue iron, measured by atomic absorption, was reduced by 20% in the liver and 25% in the heart (P < 0.01 for each organ). During the first 8 h after a D-Exo dose, iron was excreted in the urine. Mice treated with D-Exo gained weight normally and showed no evidence of toxicity. In conclusion, in this iron-overload mouse model, D-Exo administered intravenously or i.p. rapidly diffuses into multiple organs, including the heart and liver, and effectively removes iron without apparent toxicity.