Related Experiment Video
Updated: Mar 8, 2026
Author Spotlight: Advantages of Pressure-Volume Loop Measurement Method in Cardiovascular Research
Published on: January 12, 2024
Effects of digoxin on cardiac iron content in rat model of iron overload
Hamid Reza Nasri1, Beydolah Shahouzehi2, Yaser Masoumi-Ardakani3
1Associate Professor, Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.
Insights
Digoxin may increase cardiac iron accumulation in iron overload conditions, potentially worsening heart failure. Further research is needed to understand the exact mechanism and reconsider digoxin use in these patients.
Area of Science:
- Cardiology
- Pharmacology
- Toxicology
Background:
- Excess plasma iron can accumulate in vital organs like the heart, kidneys, and liver.
- Iron overload cardiomyopathy, a complication of thalassemia, leads to heart damage and heart failure.
- Digoxin, used to treat heart failure, affects intracellular sodium and calcium levels, but its interaction with iron in the heart is unclear.
Purpose of the Study:
- To investigate the effect of digoxin on cardiac iron content in a rat model of iron overload.
- To explore the potential role of digoxin in iron transport into cardiomyocytes.
Main Methods:
- Rats with iron overload were treated with varying doses of digoxin (0.5, 1, and 5 mg/kg/day) via intraperitoneal injection.
- Cardiac iron content was assessed following a 20-day treatment period.
- Pathological examination was conducted to evaluate cardiac tissue.
Main Results:
- Groups receiving iron-dextran and digoxin exhibited significantly higher cardiac iron content compared to control groups.
- Pathology assessments corroborated the increased iron accumulation in the heart.
Conclusions:
- Digoxin appears to influence iron transport into the heart during iron overload.
- L-type Ca2+ channels are potential mediators of this iron accumulation in cardiomyocytes.
- The findings suggest a need to re-evaluate digoxin's use in patients with thalassemia and iron overload conditions.
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+/Ca2+ 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 1 received four IP injections of iron-dextran (12.5mg/100g body weight) every 5 days evenly distributed over 20 days. Groups 2-4 received 0.5, 1 and 5 mg/kg/day IP digoxin, respectively. Last three groups 5-7 received iron-dextran as group 1 and digoxin concentrations 0.5, 1 and 5 mg/kg/day, respectively.
Results:
Cardiac iron contents were significantly higher in iron overload groups that received different concentrations (0.5, 1 and 5 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 Ca2+ 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.
