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TLc-A是领先的基于纳米螯合的纳米螯合剂,可在体外和体内减轻铁过载。

TLc-A, the leading nanochelating-based nanochelator, reduces iron overload in vitro and in vivo.

作者信息

Kalanaky Somayeh, Hafizi Maryam, Safari Sepideh, Mousavizadeh Kazem, Kabiri Mahboubeh, Farsinejad Alireza, Fakharzadeh Saideh, Nazaran Mohammad Hassan

机构信息

Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran.

Cancer Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Int J Hematol. 2016 Mar;103(3):274-82. doi: 10.1007/s12185-015-1932-8. Epub 2016 Feb 1.

Abstract

Iron chelation therapy is an effective approach to the treatment of iron overload conditions, in which iron builds up to toxic levels in the body and may cause organ damage. Treatments using deferoxamine, deferasirox and deferiprone have been introduced and despite their disadvantages, they remain the first-line therapeutics in iron chelation therapy. Our study aimed to compare the effectiveness of the iron chelation agent TLc-A, a nano chelator synthetized based on the novel nanochelating technology, with deferoxamine. We found that TLc-A reduced iron overload in Caco2 cell line more efficiently than deferoxamine. In rats with iron overload, very low concentrations of TLc-A lowered serum iron level after only three injections of the nanochelator, while deferoxamine was unable to reduce iron level after the same number of injections. Compared with deferoxamine, TLc-A significantly increased urinary iron excretion and reduced hepatic iron content. The toxicity study showed that the intraperitoneal median lethal dose for TLc-A was at least two times higher than that for deferoxamine. In conclusion, our in vitro and in vivo studies indicate that the novel nano chelator compound, TLc-A, offers superior performance in iron reduction than the commercially available and widely used deferoxamine.

摘要

铁螯合疗法是治疗铁过载病症的有效方法,在铁过载病症中,铁在体内蓄积至有毒水平并可能导致器官损伤。已引入使用去铁胺、地拉罗司和去铁酮的治疗方法,尽管它们存在缺点,但仍然是铁螯合疗法的一线治疗药物。我们的研究旨在比较铁螯合剂TLc-A(一种基于新型纳米螯合技术合成的纳米螯合剂)与去铁胺的有效性。我们发现,TLc-A比去铁胺更有效地降低了Caco2细胞系中的铁过载。在铁过载的大鼠中,极低浓度的TLc-A在仅注射三次纳米螯合剂后就降低了血清铁水平,而相同注射次数后去铁胺无法降低铁水平。与去铁胺相比,TLc-A显著增加尿铁排泄并降低肝脏铁含量。毒性研究表明,TLc-A的腹腔半数致死剂量至少比去铁胺高两倍。总之,我们的体外和体内研究表明,新型纳米螯合剂化合物TLc-A在降低铁水平方面比市售且广泛使用的去铁胺具有更优异的性能。

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