Effects of digoxin on cardiac iron content in rat model of iron overload

BACKGROUND: Plasma iron excess can lead to iron accumulation in heart, kidney and liver. Heart failure is a clinical widespread syndrome. In thalassemia, iron overload cardiomyopathy is caused by iron accumulation in the heart that leads to cardiac damage and heart failure. Digoxin increases the intracellular sodium concentration by inhibition of Na+/K+-ATPase that affects Na+/Ca۲+ exchanger (NCX), which raises intracellular calcium and thus attenuates heart failure. The mechanism of iron uptake into cardiomyocytes is not exactly understood. METHODS: We assessed the effect of different concentrations of digoxin on cardiac iron content in rat model of iron overload. Digoxin had been administrated intraperitoneally (IP) for one week before main study began to assure increased digoxin levels. Group ۱ received four IP injections of iron-dextran (۱۲.۵mg/۱۰۰g body weight) every ۵ days evenly distributed over ۲۰ days. Groups ۲-۴ received ۰.۵, ۱ and ۵ mg/kg/day IP digoxin, respectively. Last three groups ۵-۷ received iron-dextran as group ۱ and digoxin concentrations ۰.۵, ۱ and ۵ mg/kg/day respectively. RESULTS: Cardiac iron contents were significantly higher in iron overload groups that received different concentrations (۰.۵, ۱ and ۵ mg/kg/day) of digoxin than their counterparts in control groups and this pattern was also observed in pathology assessment. CONCLUSION: It seems that digoxin plays an important role in iron transport into heart in iron overload state but exact mechanism of this phenomenon is not clear. L-type Ca۲+ channels are good candidates that probably could be involved in iron accumulation in cardiomyocytes. Thus it would be better to reconsider digoxin administration in thalassemia and iron overload conditions 

Keywords:

Iron Overload , Digoxin , Iron Dextran Complex , Cardiac Iron Content