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去铁胺与去铁酮对大鼠慢性铁过载诱导的心脏毒性保护作用的比较研究

Comparative study of the protective effect between deferoxamine and deferiprone on chronic iron overload induced cardiotoxicity in rats.

作者信息

Emara A M, El Kelany R S, Moustafa K A

机构信息

Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Tanta University, Egypt.

出版信息

Hum Exp Toxicol. 2006 Jul;25(7):375-85. doi: 10.1191/0960327106ht637oa.

DOI:10.1191/0960327106ht637oa
PMID:16898166
Abstract

Patients with iron overload frequently suffer from hemochromatosis of major organs, such as the heart and liver. Heart affection is the most common cause of death in patients with iron overload. Although the beneficial effects of deferoxamine (DFO) on iron-associated mortality are well documented, the role of deferiprone in the management of transfusional iron overload is controversial. The aim of this study was to compare the protective effect of iron chelators (DFO and deferiprone) individually and in combination with the anti-oxidant (vitamin C) in the prevention of myocardial damage. Sixty albino rats were divided into six groups: two control groups (noniron-loaded and iron-loaded) and four iron-loaded groups classified as follows: DFO group, DFO combined with vitamin C group, deferiprone group and deferiprone combined with vitamin C group. Heart tissue and blood samples were taken for histopathological examination of the heart, determination of total iron-binding capacity, 8-OH-deoxyguanosine (8-OH-dG), myocardial lipid peroxidation and glutathione (GSH) content. Less histopathological cardiac changes and a significant decrease in all biochemical parameters, except myocardial GSH, were observed in the deferiprone group. The addition of vitamin C improves the biochemical and histopathological changes in comparison to those rats administered DFO or deferiprone individually.

摘要

铁过载患者常患有主要器官如心脏和肝脏的血色素沉着症。心脏病变是铁过载患者最常见的死亡原因。尽管去铁胺(DFO)对铁相关死亡率的有益作用已有充分记录,但去铁酮在治疗输血性铁过载中的作用仍存在争议。本研究的目的是比较铁螯合剂(DFO和去铁酮)单独使用以及与抗氧化剂(维生素C)联合使用在预防心肌损伤方面的保护作用。将60只白化大鼠分为六组:两个对照组(未铁负荷和铁负荷组)以及四个铁负荷组,分类如下:DFO组、DFO与维生素C联合组、去铁酮组和去铁酮与维生素C联合组。采集心脏组织和血液样本用于心脏的组织病理学检查、总铁结合能力、8-羟基脱氧鸟苷(8-OH-dG)、心肌脂质过氧化和谷胱甘肽(GSH)含量的测定。去铁酮组观察到较少的心脏组织病理学变化,并且除心肌GSH外,所有生化参数均显著降低。与单独给予DFO或去铁酮的大鼠相比,添加维生素C可改善生化和组织病理学变化。

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