Shahouzehi Beydolah, Nasri Hamid Reza, Masoumi-Ardakani Yaser
Assistant Professor, Student Research Committee AND Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.
Associate Professor, Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.
ARYA Atheroscler. 2018 Mar;14(2):46-52. doi: 10.22122/arya.v14i2.1642.
Thalassaemia is a hereditary disorder and has an economic burden on patients and the government. The most prevalent complication in these patients is iron overload which is followed by cardiomyopathy. Digoxin is considered as a treatment against heart failure in thalassaemia. The present study evaluated the effect of two digoxin concentrations on iron content and antioxidative defense in cardiac tissue of iron-overloaded rats.
The study was conducted on 48 rats which were divided into 6 groups. Group 1 was the control group and did not receive any treatment and group 2 was the iron overload group. In addition groups 3 and 4 were the digoxin control groups which received 1 and 5 mg/kg/day of digoxin, respectively. Groups 5 and 6 received 1 and 5 mg/kg/day of digoxin plus iron-dextran, respectively. After 1 month, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), and total antioxidant status (TAS) were assessed in cardiac tissues.
Co-administration of iron-dextran and digoxin (1 and 5 mg/kg/day) significantly increased SOD and TAS levels (P < 0.0010) and reduced MDA (P < 0.0010) in heart tissue compared to control and iron overload groups. GPX levels significantly reduced in groups 5 and 6 (iron + digoxin 1 (P < 0.0500) and iron + digoxin 5) (P < 0.0010) compared to the iron control group.
Digoxin remarkably facilitates iron uptake by cardiomyocytes by affecting other channels such as L-type and T-type Ca2+ channels (LTCC and TTCC). Digoxin administration in the iron-overloaded rat model deteriorated antioxidative parameters and increased iron entry into heart tissue at higher doses. Therefore, in patients with beta thalassaemia major, digoxin must be administered with great care and serum iron and ferritin must be regularly monitored.
地中海贫血是一种遗传性疾病，给患者和政府带来经济负担。这些患者中最常见的并发症是铁过载，其次是心肌病。地高辛被认为是治疗地中海贫血心力衰竭的药物。本研究评估了两种地高辛浓度对铁过载大鼠心脏组织铁含量和抗氧化防御的影响。
对48只大鼠进行研究，将其分为6组。第1组为对照组，未接受任何治疗，第2组为铁过载组。此外，第3组和第4组为地高辛对照组，分别接受1和5mg/kg/天的地高辛。第5组和第6组分别接受1和5mg/kg/天的地高辛加右旋糖酐铁。1个月后，评估心脏组织中的丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPX）和总抗氧化状态（TAS）。
与对照组和铁过载组相比，联合给予右旋糖酐铁和地高辛（1和5mg/kg/天）显著提高了心脏组织中SOD和TAS水平（P<0.0010），并降低了MDA（P<0.0010）。与铁对照组相比，第5组和第6组（铁+地高辛1（P<0.0500）和铁+地高辛5）（P<0.0010）的GPX水平显著降低。
地高辛通过影响其他通道，如L型和T型Ca2+通道（LTCC和TTCC），显著促进心肌细胞对铁的摄取。在铁过载大鼠模型中，给予地高辛会使抗氧化参数恶化，并在高剂量时增加铁进入心脏组织。因此，对于重型β地中海贫血患者，必须谨慎使用地高辛，并且必须定期监测血清铁和铁蛋白。
