Dexrazoxane Prevents Myocardial Ischemia/Reperfusion-Induced Oxidative Stress in the Rat Heart

Ramu, Eyal; Korach, Amit; Houminer, Esther; Schneider, Aviva; Elami, Amir; Schwalb, Herzl

doi:10.1007/s10557-006-0497-4

Cited by 17 publications

(9 citation statements)

References 32 publications

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“…Ramu et al, used the Langendorff system to perfuse isolated rat hearts with Krebs-Henseleit buffer during the course of experimental I/R injury, and showed attenuating effects of Dex [42]. This model lacks the important local and systemic effects of I/R, caused mainly by the inflammatory and coagulatory cascades in vivo.…”

Section: Discussionmentioning

confidence: 99%

Dexrazoxane Shows No Protective Effect in the Acute Phase of Reperfusion during Myocardial Infarction in Pigs

et al. 2016

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Calcium and iron overload participate in the mechanisms of ischemia/reperfusion (I/R) injury during myocardial infarction (MI). Calcium overload induces cardiomyocyte death by hypercontraction, while iron catalyses generation of reactive oxygen species (ROS). We therefore hypothesized that dexrazoxane, an intracellular metal chelator, would attenuate I/R injury. MI was induced in pigs by occlusion of the left anterior descending artery for 1 hour followed by 2 hours reperfusion. Thirty minutes before reperfusion either 5 mg/ml dexrazoxane (n = 5) or saline (n = 5) was infused intravenously. Myocardial necrosis as percentage of the area at ischemic risk was found to be similar in both groups (77.2 ± 18% for dexrazoxane and 76.4 ± 14% for saline group) as determined by triphenyl tetrazolium chloride staining of the ischemic myocardium. Also, serum levels of troponin-I were similar in both groups. A conductance catheter was used to measure left ventricular pressure and volume at all times. Markers for tissue damage due to ROS (HNE), endothelial cell activation (CD31) and inflammation (IgG, C3b/c, C5b9, MCP-1) were assessed on tissue and/or in serum. No significant differences were observed between the groups for the parameters analyzed. To conclude, in this clinically relevant model of early reperfusion after acute myocardial ischemia, dexrazoxane lacked attenuating effects on I/R injury as shown by the measured parameters.

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Section: Discussionmentioning

confidence: 99%

Dexrazoxane Shows No Protective Effect in the Acute Phase of Reperfusion during Myocardial Infarction in Pigs

et al. 2016

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“…Hasinoff reported that DZR was highly effective in protecting cultured neonatal rat cardiomyocytes from hypoxiareoxygenation-induced damage through decreasing intracellular lactate dehydrogenase release [14]. Ramu reported that DZR significantly inhibited I/R injury, decreased protein carbonylation and improved hemodynamic recovery by decreasing free radical formation in an isolated perfused rat heart [15]. However, the effect of DZR on MI has not been well explored.…”

Section: Introductionmentioning

confidence: 99%

Cardioprotective effect of dexrazoxane in a rat model of myocardial infarction: Anti-apoptosis and promoting angiogenesis

Zhou

Sung

et al. 2011

International Journal of Cardiology

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“…Consistently with these results, pharmacological interventions, such as iron chelation, have also shown effective protection against iron-dependent processes of cell death. It has been demonstrated that iron chelator dexrazoxane (DZX), as a mitochondria-permeable metal chelator, decreased free radicals’ generation and improved post-I/R hemodynamics in the ex vivo rat hearts [ 152 ]. In addition, DZX protected mice against DOX-induced ferroptosis and reduced lethal heart injury (size of infarction) and myocardial dysfunction following I/R [ 77 ].…”

Section: Iron and Ferroptosis: A Less-known Form Of Cell Death Andmentioning

confidence: 99%

The Molecular Mechanisms of Iron Metabolism and Its Role in Cardiac Dysfunction and Cardioprotection

Ravingerová

Kindernay

Barteková

et al. 2020

IJMS

111

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Iron is an essential mineral participating in different functions of the organism under physiological conditions. Numerous biological processes, such as oxygen and lipid metabolism, protein production, cellular respiration, and DNA synthesis, require the presence of iron, and mitochondria play an important role in the processes of iron metabolism. In addition to its physiological role, iron may be also involved in the adaptive processes of myocardial “conditioning”. On the other hand, disorders of iron metabolism are involved in the pathological mechanisms of the most common human diseases and include a wide range of them, such as type 2 diabetes, obesity, and non-alcoholic fatty liver disease, and accelerate the development of atherosclerosis. Furthermore, iron also exerts potentially deleterious effects that may be manifested under conditions of ischemia/reperfusion (I/R) injury, myocardial infarction, heart failure, coronary artery angioplasty, or heart transplantation, due to its involvement in reactive oxygen species (ROS) production. Moreover, iron has been recently described to participate in the mechanisms of iron-dependent cell death defined as “ferroptosis”. Ferroptosis is a form of regulated cell death that is distinct from apoptosis, necroptosis, and other types of cell death. Ferroptosis has been shown to be associated with I/R injury and several other cardiac diseases as a significant form of cell death in cardiomyocytes. In this review, we will discuss the role of iron in cardiovascular diseases, especially in myocardial I/R injury, and protective mechanisms stimulated by different forms of “conditioning” with a special emphasis on the novel targets for cardioprotection.

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Dexrazoxane Prevents Myocardial Ischemia/Reperfusion-Induced Oxidative Stress in the Rat Heart

Abstract: The decrease in proteins carbonylation and correlative hemodynamic improvement suggests that Dex decreases I/R free radical formation and reperfusion injury.

Cited by 17 publications

References 32 publications

Dexrazoxane Shows No Protective Effect in the Acute Phase of Reperfusion during Myocardial Infarction in Pigs

Dexrazoxane Shows No Protective Effect in the Acute Phase of Reperfusion during Myocardial Infarction in Pigs

Cardioprotective effect of dexrazoxane in a rat model of myocardial infarction: Anti-apoptosis and promoting angiogenesis

The Molecular Mechanisms of Iron Metabolism and Its Role in Cardiac Dysfunction and Cardioprotection

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