Related Experiment Video
Updated: Jun 1, 2026
Measurement of Tissue Non-Heme Iron Content using a Bathophenanthroline-Based Colorimetric Assay
Published on: January 31, 2022
Establishment of secondary iron overloaded mouse model: evaluation of cardiac function and analysis according to iron
Se Na Moon1, Ji Whan Han, Hui Seung Hwang
1Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea. kshs13@catholic.ac.kr
Insights
Secondary iron overload from blood transfusions damages heart function. This study developed a mouse model showing iron deposition correlates with cardiac changes, aiding research into iron chelation therapy.
Area of Science:
- Cardiology
- Hematology
- Toxicology
Background:
- Periodic blood transfusions in hematologic and oncologic diseases can cause secondary iron overload.
- Iron deposition in cardiac tissue impairs heart function, leading to dilated cardiomyopathy and heart failure.
Purpose of the Study:
- To establish a murine model of secondary iron overload.
- To investigate cardiac function changes and histopathologic alterations in this model.
Main Methods:
- C57/BL mice received daily iron dextran injections for 2, 4, or 6 weeks.
- Cardiac function was assessed using echocardiography.
- Plasma iron, liver iron content, and cardiac/liver histopathology were examined.
Main Results:
- Echocardiography revealed interventricular septum and posterior wall thickening correlated with iron dose (P < 0.01).
- Left ventricular end-diastolic volume increased in the highest iron dose group (300 mg, P < 0.01).
- Plasma and liver iron levels, along with histopathologic iron deposition, increased proportionally with cumulative iron dose.
Conclusions:
- The established murine model effectively mimics secondary iron overload and associated cardiac changes.
- This model aids in understanding the pathophysiology of cardiomyopathy in iron-overloaded patients.
- The model is suitable for evaluating in vivo iron-chelating therapies.
Abstract:
Periodic blood transfusion can lead to secondary iron overload in patients with hematologic and oncologic diseases. Iron overload can result in iron deposition in heart tissue, which decreases cardiac function and can ultimately lead to death due to dilated cardiomyopathy and cardiac failure. In this study, we established murine model of secondary iron overload, studied the changes in cardiac function with echocardiography, and examined the histopathologic changes. Three experimental groups of the six week-old C57/BL mice (H-2(b)) were injected intraperitoneally with 10 mg of iron dextran daily 5 days a week for 2, 4, and 6 weeks. Cumulative doses of iron for the three experimental groups were 100, 200, and 300 mg, while the control groups were injected with the same amounts of phosphate-buffered saline. We studied the cardiac function under anesthesia with echocardiography using a GE Vivid7 Dimension system. Plasma iron levels and liver iron contents were measured. The hearts and livers were harvested and stained with H&E and Perls Prussian blue for iron, and the levels of iron deposit were examined. We assessed the cardiac measurements after adjustment for weight. On echocardiography, thicknesses of the interventricular septum and posterior ventricular wall (PS) during diastole showed correlation with the amount of iron deposit (P < 0.01). End-diastolic volume showed dilatation of the left ventricle in the 300 mg group (P < 0.01). Changes in the fractional shortening were not statistically significant (P = 0.07). Plasma iron levels and liver iron contents were increased proportionally according to the amount of iron loaded. The histopathologic findings of PS and liver showed higher grade of iron deposit proportional to the cumulated iron dose. In this study, we present an animal model which helps understand the cardiac function changes in patients with secondary iron overload due to repeated blood transfusions. Our results may help characterize the pathophysiologic features of cardiomyopathy in patients with secondary iron overload, and our model may be applied to in vivo iron-chelating therapy studies.
