Current and future treatment strategies for iron overload cardiomyopathy

Wongjaikam, Suwakon; Kumfu, Sirinart; Chattipakorn, Nipon; Fucharoen, Suthat

doi:10.1016/j.ejphar.2015.08.017

Cited by 37 publications

(34 citation statements)

References 57 publications

(91 reference statements)

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“…Recently, combined treatment with oral deferiprone and subcutaneous desferoxamine twice weekly was shown to be a safe and effective alternative to chelation monotherapy in transfusion-dependent beta-thalassemia children [33]. The use of combined Fe chelators to prevent Fe-overload cardiomyopathy in thalassemia has been reported [34, 35]. Moreover, deferiprone is considered similar to deferoxamine in the treatment of thalassemia intermedia [36].…”

Section: Chelating Agentsmentioning

confidence: 99%

Rationale for the Successful Management of EDTA Chelation Therapy in Human Burden by Toxic Metals

Ferrero

2016

BioMed Research International

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Exposure to environmental and occupational toxicants is responsible for adverse effects on human health. Chelation therapy is the only procedure able to remove toxic metals from human organs and tissue, aiming to treat damage related to acute and/or chronic intoxication. The present review focuses on the most recent evidence of the successful use of the chelating agent ethylenediaminetetraacetic acid (EDTA). Assessment of toxic-metal presence in humans, as well as the rationale of EDTA therapy in cardiovascular and neurodegenerative diseases, is reported.

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Section: Chelating Agentsmentioning

confidence: 99%

Rationale for the Successful Management of EDTA Chelation Therapy in Human Burden by Toxic Metals

Ferrero

2016

BioMed Research International

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“…55,[60][61][62][63][64][65] However, it has been suggested that combined chelation therapy be used in some iron overload b-thalassemia patients who have shown no improvement when treated with a single iron chelator, due to its increased efficacy. [62][63][64][65] At this time, new evidence indicates a greater efficacy for iron chelation when an iron chelator was combined with an antioxidant such as vitamin E and N-acetylcysteine (NAC). 66,67 Combined iron chelator plus NAC shows greater efficacy than vitamin E in reducing DNA damage in children b-thalassemia patients.…”

Section: Cardiac Complications In Beta-thalassemia Patientsmentioning

confidence: 99%

Cardiac complications in beta-thalassemia: From mice to men

Kumfu

Fucharoen

Chattipakorn

2017

Exp Biol Med (Maywood)

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Iron overload cardiomyopathy is a major cause of morbidity and mortality in patients with thalassemia. Since investigation of iron overload cardiomyopathy in thalassemia patients has many limitations, a search for an animal model for this condition has been ongoing for decades. In the past decades, there is no doubt that the use of b-thalassemic mice as a study model to investigate the pathophysiology of iron overload cardiomyopathy and the role of various pharmacological interventions, has shed some light in understanding this serious complication and in improving the associated cardiac dysfunction. In this review, the effects of iron overload on the hearts of b-thalassemic mice under conditions of iron overload as well as the efficacy of pharmacological interventions to combat these adverse effects on the heart are reviewed and discussed. AbstractBeta-thalassemia is an inherited hemoglobin disorder caused by reduced or absent synthesis of the beta globin chains of hemoglobin. This results in variable outcomes ranging from clinically asymptomatic to severe anemia, which then typically requires regular blood transfusion. These regular blood transfusions can result in an iron overload condition. The iron overload condition can lead to iron accumulation in various organs, especially in the heart, leading to iron overload cardiomyopathy, which is the major cause of mortality in patients with thalassemia. In the past decades, there is no doubt that the use of b-thalassemic mice as a study model to investigate the pathophysiology of iron overload cardiomyopathy and the role of various pharmacological interventions, has shed some light in understanding this serious complication and in improving the associated cardiac dysfunction. In this review, the effects that iron overload has on the hearts of b-thalassemic mice under conditions of iron overload as well as the efficacy of pharmacological interventions to combat these adverse effects on the heart are reviewed and discussed. The in-depth understanding of biomolecular alterations in the heart of these iron overload thalassemic mice will help give guidance for more effective therapeutic approaches in the near future.

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“…Excess plasma NTBI and LPI leads to iron overload, both systemically and within tissues, resulting in increased reactive oxygen species (ROS) via Haber-Weiss and Fenton’s reactions67. Increased ROS is a major cause of tissue and organ damage, particularly in the heart612. Plasma NTBI and LPI can rapidly enter cardiomyocytes, resulting in increased free iron or labile cellular iron, which causes increased cardiac oxidative stress and iron overload cardiomyopathy7.…”

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confidence: 99%

Restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and N-acetyl cysteine

Wongjaikam

Kumfu

Khamseekaew

et al. 2017

Sci Rep

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Intracellular calcium [Ca2+]i dysregulation plays an important role in the pathophysiology of iron overload cardiomyopathy. Although either iron chelators or antioxidants provide cardioprotection, a comparison of the efficacy of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), N-acetyl cysteine (NAC) or a combination of DFP plus NAC on cardiac [Ca2+]i homeostasis in chronic iron overload has never been investigated. Male Wistar rats were fed with either a normal diet or a high iron (HFe) diet for 4 months. At 2 months, HFe rats were divided into 6 groups and treated with either a vehicle, DFO (25 mg/kg/day), DFP (75 mg/kg/day), DFX (20 mg/kg/day), NAC (100 mg/kg/day), or combined DFP plus NAC. At 4 months, the number of cardiac T-type calcium channels was increased, whereas cardiac sarcoplasmic-endoplasmic reticulum Ca2+ ATPase (SERCA) was decreased, leading to cardiac iron overload and impaired cardiac [Ca2+]i homeostasis. All pharmacological interventions restored SERCA levels. Although DFO, DFP, DFX or NAC alone shared similar efficacy in improving cardiac [Ca2+]i homeostasis, only DFP + NAC restored cardiac [Ca2+]i homeostasis, leading to restoring left ventricular function in the HFe-fed rats. Thus, the combined DFP + NAC was more effective than any monotherapy in restoring cardiac [Ca2+]i homeostasis, leading to restored myocardial contractility in iron-overloaded rats.

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Current and future treatment strategies for iron overload cardiomyopathy

Cited by 37 publications

References 57 publications

Rationale for the Successful Management of EDTA Chelation Therapy in Human Burden by Toxic Metals

Rationale for the Successful Management of EDTA Chelation Therapy in Human Burden by Toxic Metals

Cardiac complications in beta-thalassemia: From mice to men

Restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and N-acetyl cysteine

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