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Deferiprone protects the isolated atria from cardiotoxicity induced by doxorubicin

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Abstract:

Abstract

Aim: To investigate the effects of deferiprone on doxorubicin-induced cardiotoxicity and determine its protection on cardiac contractility in vivo at tissue level. Methods: Spontaneously-beating isolated atria from rats were pre-treated with deferiprone for 10minat 1.2mmol/L or 0.3 mmol/L, respectively before co-incubation with doxorubicin (DOX) at 0.03 mmol/L for 60 min. Contractility (d F/dt) was assessed every 10 min during the incubation. After that, the tissues around the sinuatrial nodes were fixed for ultrastructural study; succinate dehy-drogenase (SDH) and Cu, Zn superoxide dismutase (Cu, Zn-SOD) activity, as well as malondialdehyde (MDA) level of the atria were assayed. Results: Treatment with DOX alone resulted in a 49.34% reduction of the contractility, mitochondria swelling, disruption of mitochondrial crista and decreased electron density of the matrices. Conversely, with the presence of deferiprone, the negative inotropic effect and lesions in the cardiac mitochondria structure induced by DOX were attenuated. Cu, Zn-SOD activity increased by 12.97%–12.11%, the MDA level decreased by 29.12%–39.82% and succinate dehydrogenase (SDH) activity was ameliorated by 25.15%–34.76%. Conclusion: Deferiprone can efficiently preserve cardiac contractility. Moreover, the results of this study indicate that deferiprone is able to protect mitochondrial function and structure form damage induced by DOX. This cardiac protective potential of deferiprone could be due to its defense capability against oxidative damage.

Keywords: cardiac protection; cardiotoxicity; deferiprone; doxorubicin; isolated atria

Document Type: Research Article

DOI: https://doi.org/10.1111/j.1745-7254.2006.00409.x

Affiliations: 1: Fudan-PharmCo Drug Targeting Research Center, Department of Pharmaceutics, Fudan University, Shanghai 200032, China 2: Department of Pharmacology, Fudan University, Shanghai 200032, China 3: School of Pharmacy, Fudan University, Shanghai 200032, China

Publication date: 2006-10-01

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