Navidi-Shishaone Mitra, Mohhebi Soheila, Nematbakhsh Mehdi, Roozbehani Shahla, Talebi Ardeshir, Pezeshki Zahra, Eshraghi-Jazi Fatemeh, Mazaheri Safoora, Shirdavani Sohiela, Gharagozloo Marjan, Moaeidi Behjat Alsaadat
Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran ; Department of Biology, Falavarjan Branch, Islamic Azad University, Isfahan, Iran.
Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran ; Department of Physiology, Isfahan University of Medical Science, Isfahan, Iran ; Isfahan Institute of Basic and Applied Sciences Research, Isfahan, Iran.
Int J Prev Med. 2014 Jan;5(1):110-6.
Tissue iron deposition may disturb functions of the organs. In many diseases like thalassemia, the patients suffer from iron deposition in kidney and heart tissues. Deferoxamine (DF) is a synthetic iron chelator and silymarin (SM) is an antioxidant and also a candidate for iron chelating. This study was designed to investigate the effect of DF and SM combination against kidney and heart iron deposition in an iron overload rat model.
Male Wistar rats were randomly assigned to 5 groups. The iron overloading was performed by iron dextran 100 mg/kg/day every other day during 2 weeks and in the 3(rd) week, iron dextran was discontinued and the animals were treated daily with combination of SM (200 mg/kg/day, i.p.) and DF (50 mg/kg/day, i.p.) (group 1), SM (group 2), DF (group 3) and saline (group 4). Group 5 received saline during the experiment. Finally, blood samples were obtained and kidney, heart and liver were immediately removed and prepared for histopathological procedures.
The results indicated no significant difference in kidney function and endothelial function biomarkers between the groups. However, combination of SM and DF did not attenuate the iron deposition in the kidney, liver and heart. DF alone, rather than DF and SM combination, significantly reduced the serum level of malondialdehyde (P < 0.05). Co-administration of SM and DF significantly increased the serum level of ferritin (P < 0.05).
DF and SM may be potentially considered as iron chelators. However, combination of these two agents did not provide a protective effect against kidney, liver and heart iron deposition.
组织铁沉积可能会干扰器官功能。在许多疾病如地中海贫血中,患者会出现肾脏和心脏组织的铁沉积。去铁胺(DF)是一种合成铁螯合剂,水飞蓟素(SM)是一种抗氧化剂,也是铁螯合的候选药物。本研究旨在探讨DF和SM联合使用对铁过载大鼠模型肾脏和心脏铁沉积的影响。
将雄性Wistar大鼠随机分为5组。在2周内每隔一天通过腹腔注射100 mg/kg/天的右旋糖酐铁进行铁过载处理,在第3周停止注射右旋糖酐铁,然后对动物每天进行SM(200 mg/kg/天,腹腔注射)和DF(50 mg/kg/天,腹腔注射)联合治疗(第1组)、SM治疗(第2组)、DF治疗(第3组)和生理盐水治疗(第4组)。第5组在实验期间接受生理盐水。最后,采集血样,立即取出肾脏、心脏和肝脏,准备进行组织病理学检查。
结果表明,各组之间的肾功能和内皮功能生物标志物无显著差异。然而,SM和DF联合使用并未减轻肾脏、肝脏和心脏的铁沉积。单独使用DF而非DF与SM联合使用能显著降低血清丙二醛水平(P < 0.05)。SM和DF联合使用显著提高了血清铁蛋白水平(P < 0.05)。
DF和SM可能被潜在地视为铁螯合剂。然而,这两种药物联合使用并未对肾脏、肝脏和心脏的铁沉积提供保护作用。