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Reversal of cardiac iron loading and dysfunction in thalassemic mice by curcuminoids
C Thephinlap1, C Phisalaphong, N Lailerd
1Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Insights
Curcuminoids (CUR) effectively reduce harmful non-transferrin bound iron (NTBI) and iron in the heart. This treatment alleviates oxidative stress and improves cardiac function in iron-loaded thalassemic mice.
Area of Science:
- Biochemistry
- Cardiology
- Pharmacology
Background:
- Non-transferrin bound iron (NTBI) in thalassemia patients causes oxidative damage, particularly cardiac siderosis.
- Current iron chelators like DFP show efficacy, but novel treatments are explored.
- Curcuminoids (CUR) possess iron-chelating and antioxidant properties.
Purpose of the Study:
- To investigate the effects of curcuminoids (CUR) on cardiac iron deposition and function in iron-loaded mice.
- To assess CUR's ability to reduce plasma NTBI and myocardial iron accumulation.
- To evaluate CUR's impact on oxidative stress and cardiac autonomic function.
Main Methods:
- Iron-loaded wild type and beta-knockout mice were treated with CUR and deferiprone (DFP).
- Plasma NTBI and malondialdehyde (MDA) levels were measured using HPLC.
- Heart iron concentration, ECG, and heart rate variability (HRV) were assessed.
Main Results:
- Ferric (Fe) diet increased plasma NTBI, MDA, and heart iron, while decreasing HRV.
- CUR and DFP treatments significantly reduced plasma NTBI and MDA levels.
- Both CUR and DFP effectively lowered heart iron accumulation and improved HRV.
Conclusions:
- Curcuminoids (CUR) demonstrate efficacy in reducing plasma NTBI and myocardial iron.
- CUR alleviates lipid peroxidation and improves cardiac autonomic function in iron-loaded thalassemic models.
- CUR represents a potential therapeutic agent for managing iron overload in thalassemia.
Abstract:
Non-transferrin bound iron (NTBI) is found in plasma of β-thalassemia patients and causes oxidative tissue damage. Cardiac siderosis and complications are the secondary cause of death in β-thalassemia major patients. Desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) are promising chelators used to get negative iron balance and improve life quality. DFP has been shown to remove myocardial iron effectively. Curcuminoids (CUR) can chelate plasma NTBI, inhibit lipid peroxidation and alleviate cardiac autonomic imbalance. Effects of CUR on cardiac iron deposition and function were investigated in iron-loaded mice. Wild type ((mu)β(+/+) WT) and heterozygous β-knockout ((mu)β(th-3/+) BKO) mice (C57BL/6) were fed with ferrocene-supplemented diet (Fe diet) and coincidently intervened with CUR and DFP for 2 months. Concentrations of plasma NTBI and malondialdehyde (MDA) were measured using HPLC techniques. Heart iron concentration was determined based on atomic absorption spectrophotometry and Perl's staining methods. Short-term electrocardiogram (ECG) was recorded with AD Instruments Power Lab, and heart rate variability (HRV) was evaluated using MATLAB 7.0 program. Fe diet increased levels of NTBI and MDA in plasma, nonheme iron and iron deposit in heart tissue significantly, and depressed the HRV, which the levels were higher in the BKO mice than the WT mice. CUR and DFP treatments lowered plasma NTBI as well as MDA concentrations (p <0.05), heart iron accumulation effectively, and also improved the HRV in the treated mice. The results imply that CUR would be effective in decreasing plasma NTBI and myocardial iron, alleviating lipid peroxidation and improving cardiac function in iron-loaded thalassemic mice.
