The iron-loaded gerbil model revisited: effects of deferoxamine and deferiprone treatment.

C. Hershko, G. Link, A. Konijn, M. Huerta, E. Rosenmann, C. Reinus
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引用次数: 31

Abstract

Although the beneficial effects of deferoxamine (DFO) on iron-associated morbidity and mortality are well documented, the role of deferiprone (L1) in the management of transfusional iron overload is controversial. This debate involves not only the question of efficacy but also of safety, with particular emphasis on the risk of a paradoxical aggravation of iron toxicity by L1. We used the iron-loaded gerbil model introduced by Carthew et al to compare the chelating efficacy of L1, DFO, or both in two gerbil strains treated by means of weekly iron-dextran injections: Psammomys obesus and pathogen-free Mongolian gerbils (Meriones unguiculatus). The difference between the high mortality and advanced hepatocellular necrosis observed in iron-loaded P obesus and the absence of mortality and limited morbidity encountered in pathogen-free Mongolian gerbils is most likely explained by the prevention of coincidental laboratory infections in the latter group. Iron-chelating treatment in all experimental groups resulted in a significant decrease in hepatic iron concentrations and normalization of mitochondrial respiratory enzyme activities, with combined L1 and DFO treatment being the most efficient, followed, in decreasing order, by DFO and L1 as single-drug treatments. Judged by tissue iron concentrations, mitochondrial enzyme activity, and hepatic histology, we could find no evidence of a paradoxical aggravation of iron toxicity by L1 in either of the two series of studies. Although these data appear to be reassuring, the present controversy related to the role of L1 in the development of hepatic cirrhosis should be eventually settled by clinical studies evaluating the effects of long-term iron-chelating treatment.
重访含铁沙鼠模型:去铁胺和去铁素治疗的效果。
虽然去铁胺(DFO)对铁相关发病率和死亡率的有益作用已得到充分证实,但去铁素(L1)在处理输注铁过载中的作用仍存在争议。这一争论不仅涉及疗效问题,还涉及安全性问题,特别强调L1对铁毒性的矛盾加重风险。我们使用Carthew等人引入的铁负载沙鼠模型,比较每周注射铁葡聚糖治疗的两种沙鼠菌株:沙母沙鼠(Psammomys obesus)和无病原体蒙古沙鼠(Meriones unguiculatus) L1、DFO或两者的螯合效果。在含铁沙鼠中观察到的高死亡率和晚期肝细胞坏死与在无病原体的蒙古沙鼠中观察到的无死亡率和有限发病率之间的差异,最有可能的解释是后者预防了偶然的实验室感染。所有实验组的铁螯合治疗均显著降低肝脏铁浓度并使线粒体呼吸酶活性正常化,其中L1和DFO联合治疗效果最好,DFO和L1单药治疗效果次之。根据组织铁浓度、线粒体酶活性和肝脏组织学判断,我们没有发现两个系列研究中L1对铁毒性的矛盾加重的证据。尽管这些数据似乎令人放心,但目前关于L1在肝硬化发展中的作用的争议应该最终通过评估长期铁螯合治疗效果的临床研究来解决。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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