Q50, an Iron-Chelating and Zinc-Complexing Agent, Improves Cardiac Function in Rat Models of Ischemia/Reperfusion-Induced Myocardial Injury

Korkmaz, Sevil; Barnucz, Enikő; Loganathan, Sivakkanan; Li, Shiliang; Radovits, Tamás; Hegedűs, Péter; Hirschberg, Kristóf; Weymann, Alexander; Puskás, László G.; Ózsvári, Béla; Faragó, Nóra; Kanizsai, Iván; Fábián, Gabriella; Gyuris, Márió; Merkely, Béla; Kretzler, Matthias; Szabó, Csaba; Szabó, Gábor

doi:10.1253/circj.cj-12-1162

Cited by 12 publications

(8 citation statements)

References 30 publications

(21 reference statements)

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“…It has been postulated that iron homeostasis could play an important role in the development of MRI in the cardiomyocytes[ 32 , 33 ]. Free iron is deleterious for cells; thus generally it is bound to proteins forming complexes[ 34 ].…”

Section: Pathophysiologymentioning

confidence: 99%

Myocardial reperfusion injury and oxidative stress: Therapeutic opportunities

González-Montero

Brito

Gajardo

et al. 2018

WJC

134

105

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Acute myocardial infarction (AMI) is the leading cause of death worldwide. Its associated mortality, morbidity and complications have significantly decreased with the development of interventional cardiology and percutaneous coronary angioplasty (PCA) treatment, which quickly and effectively restore the blood flow to the area previously subjected to ischemia. Paradoxically, the restoration of blood flow to the ischemic zone leads to a massive production of reactive oxygen species (ROS) which generate rapid and severe damage to biomolecules, generating a phenomenon called myocardial reperfusion injury (MRI). In the clinical setting, MRI is associated with multiple complications such as lethal reperfusion, no-reflow, myocardial stunning, and reperfusion arrhythmias. Despite significant advances in the understanding of the mechanisms accounting for the myocardial ischemia reperfusion injury, it remains an unsolved problem. Although promising results have been obtained in experimental studies (mainly in animal models), these benefits have not been translated into clinical settings. Thus, clinical trials have failed to find benefits from any therapy to prevent MRI. There is major evidence with respect to the contribution of oxidative stress to MRI in cardiovascular diseases. The lack of consistency between basic studies and clinical trials is not solely based on the diversity inherent in epidemiology but is also a result of the methodological weaknesses of some studies. It is quite possible that pharmacological issues, such as doses, active ingredients, bioavailability, routes of administration, co-therapies, startup time of the drug intervention, and its continuity may also have some responsibility for the lack of consistency between different studies. Furthermore, the administration of high ascorbate doses prior to reperfusion appears to be a safe and rational therapy against the development of oxidative damage associated with myocardial reperfusion. In addition, the association with N-acetylcysteine (a glutathione donor) and deferoxamine (an iron chelator) could improve the antioxidant cardioprotection by ascorbate, making it even more effective in preventing myocardial reperfusion damage associated with PCA following AMI.

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Section: Pathophysiologymentioning

confidence: 99%

Myocardial reperfusion injury and oxidative stress: Therapeutic opportunities

González-Montero

Brito

Gajardo

et al. 2018

WJC

134

105

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“…This metal oxidation process significantly lowered oxygen oxidation to become reactive oxygen. [ 3 ] In many cases with impaired oxidant-antioxidant mechanisms, administrating an iron chelatorwill improve the prognosis of various disorders, including neurodegenerative disease[ 32 ], cardiovascular impairment[ 33 ], and iron overload. [ 34 35 ] Thus, the presence of varying levels of SOD may be interfered with by the effect of iron chelation management and diet, although other inflammatory factors cannot be ruled out.…”

Section: Discussionmentioning

confidence: 99%

Status of Superoxide dismutase in transfusion dependent thalassaemia

2015

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Background:Thalassemia is a collection of genetic impairments in beta and alpha genes causing various states of anemia. Severe types of the disease need lifelong transfusions, leading to oxidant-antioxidant disturbance due to massive iron deposits.Aims:The aim of this study was to assess the antioxidant enzyme Superoxide Dismutase (SOD) and ferritin levels of thalassemia major patients in a peripheral health facility.Materials and Methods:Two hundred and nine probands were recruited and performed laboratory experiments for SOD and Ferritin levels. Chelation administration and clinical score were taken from interviewing the family and from medical report data.Results:The study showed that SOD intensity was lower (162.41 u/ml) compared to the normal cutoff point (P = 0.001), while the mean of Ferritin levels was ten times over the normal value (4226,67 ng/dl). Observations also reported that chelation medicine was not administrated properly.Conclusions:The data indicates that thalassemic patients have oxidant-antioxidant uproar due to oxidative stress. Monitored chelating administration, selective antioxidant, and a well-balanced diet may prevent oxidative injury.

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“…Langendorff models with myocardial iron overload develop different functional, biochemical and ultrastructural alterations as compared to control groups of myocardial I/R, which are prevented by deferoxamine (DFO), an iron chelator [87], realizing the harmful tissue effect of Fe high levels. The role of Fe in the postischemia MRI has been demonstrated in experimental models by the use of iron chelators at the onset of reperfusion, improving cardiac function relative to control group [88,89]. Furthermore, a long-term study conducted in randomly selected men aged 42, 48, 54 and 60, who had no symptoms of coronary heart disease at entry, showed that elevated levels of serum ferritin (stored Fe) was a strong risk factor for developing AMI [90].…”

Section: Deferoxaminementioning

confidence: 99%

Novel Antioxidant Therapy Against Myocardial Ischemia– Reperfusion Injury During Percutaneous Coronary Angioplasty

Parra¹,

Rodrigo²

2016

Free Radicals and Diseases

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Acute myocardial infarction (AMI) is the leading cause of mortality worldwide. Major advances in the treatment have included coronary interventions, such as systemic thrombolysis and percutaneous coronary angioplasty (PCA). These procedures have been aimed to recover the blood flow in the cardiac zones affected by the occlusion of a branch of the coronary artery. However, damage is generated in the heart tissue known as myocardial reperfusion injury, an event associated with increased oxidative stress. Reactive oxygen species (ROS) are able to trigger cell death pathways, and myocardial structural and functional impairment. Studies on animal models of AMI suggest that lethal reperfusion accounts for up to 50% of the final size of a myocardial infarct, a part of the damage likely to be prevented. Although a number of strategies have been aimed to ameliorate lethal reperfusion injury, up to date the beneficial effects in clinical settings remain elusive. The accumulated body of evidence suggests that redox balance is a crucial determinant of ischemia-reperfusion injury, with clear mechanistic insights into pharmacological approaches. This chapter presents the molecular basis for a novel cardioprotection of patients with AMI subjected to PCA, based on a reinforcement of the antioxidant system.

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Q50, an Iron-Chelating and Zinc-Complexing Agent, Improves Cardiac Function in Rat Models of Ischemia/Reperfusion-Induced Myocardial Injury

Cited by 12 publications

References 30 publications

Myocardial reperfusion injury and oxidative stress: Therapeutic opportunities

Myocardial reperfusion injury and oxidative stress: Therapeutic opportunities

Status of Superoxide dismutase in transfusion dependent thalassaemia

Novel Antioxidant Therapy Against Myocardial Ischemia– Reperfusion Injury During Percutaneous Coronary Angioplasty

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