Early and delayed cardioprotective intervention with dexrazoxane each show different potential for prevention of chronic anthracycline cardiotoxicity in rabbits

Jirkovský, Eduard; Lenčová-Popelová, Olga; Hroch, Miloš; Adamcová, Michaela; Mazurová, Y; Vávrová, Jaroslava; Mičuda, Stanislav; Šimůnek, Tomáš; Geršl, Vladimír; Štěrba, Martin

doi:10.1016/j.tox.2013.06.012

Cited by 30 publications

(37 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Of note, a recent experimental study has shown that the cardioprotective effect of dexrazoxane is more accentuated when administered before the first dose of anthracycline rather than after a cumulative dose of 300 mg/m 2 , suggesting that the currently recommended delayed intervention may not be able to take advantage of the full cardioprotective potential of the drug. 66 Enalapril did not prevent LVEF decline when administered during chemotherapy in a small study 67 but had marked effects when administered 1 month after the end of the last chemotherapy cycle in selected high-risk patients with positive troponin levels but normal LVEF 68 ( Table 2). An ongoing trial is comparing the efficacy of both strategies (http://www.clinicaltrials.gov; NCT01968200).…”

Section: Administration Of Cardioprotective Drugsmentioning

confidence: 96%

Myocardial Protection During Cardiotoxic Chemotherapy

Witteles

Bosch

2015

Circulation

View full text Add to dashboard Cite

Section: Administration Of Cardioprotective Drugsmentioning

confidence: 96%

Myocardial Protection During Cardiotoxic Chemotherapy

Witteles

Bosch

2015

Circulation

View full text Add to dashboard Cite

“…DEX has been shown to reduce DXR-induced oxidative stress processes and apoptosis in cardiomyocytes. Preclinical and clinical studies conferred a protective role for DEX on cardiac function devoid of any effect on the rate of response to chemotherapy or on overall survival of the treated patient (Cvetković & Scott 2005, Jirkovský et al 2013. DEX, which was originally developed as an antitumor agent, belongs to a class of molecules, bis (2,6-dioxopiperazines), known to function as topoisomerase II (TopoII) catalytic inhibitors and differs from the classical anti-cancer agents such as anthracyclins (Andoh & Ishida 1998).…”

Section: Introductionmentioning

confidence: 99%

Dexrazoxane exacerbates doxorubicin-induced testicular toxicity

Levi¹,

Tzabari²,

Savion³

et al. 2015

Reproduction

View full text Add to dashboard Cite

Infertility induced by anti-cancer treatments pose a major concern for cancer survivors. Doxorubicin (DXR) has been previously shown to exert toxic effects on the testicular germinal epithelium. Based upon the cardioprotective traits of dexrazoxane (DEX), we studied its potential effect in reducing DXR-induced testicular toxicity. Male mice were injected with 5 mg/kg DXR, 100 mg/kg DEX, combination of both or saline (control) and sacrificed either 1, 3 or 6 months later. Testes were excised and further processed. Glutathione and apoptosis assays were performed to determine oxidative stress. Immunohistochemistry and confocal microscopy were used to study the effects of the drugs on testicular histology and on spermatogonial reserve. DXR and the combined treatment induced a striking decline in testicular weight. DEX prevented DXR-induced oxidative stress, but enhanced DXR-induced apoptosis within the testes. Furthermore, the combined treatment depleted the spermatogonial reserve after 1 month, with impaired recovery at 3 and 6 months post-treatment. This resulted in compromised sperm parameters, testicular and epididymal weights as well as significantly reduced sperm motility, all of which were more severe than those observed in DXR-treated mice. The activity of DEX in the testis may differ from its activity in cardiomyocytes. Adding DEX to DXR exacerbates DXR-induced testicular toxicity. Reproduction (2015) 150 357-366

show abstract

“…The major benefit of advances in imaging is likely to be in the assessment of analogs with lower cardiotoxicity and with agents that reduce the cardiotoxicity of well-established agents and chemotherapeutic regimens. 54 Examples of this strategy include the assessment of anthracycline analogs targeting the Top2α isoenzyme, which may be less cardiotoxic, agents such as dexrazoxane, 55 and an engineered bivalent neuregulin-1β, which reduces toxicity in doxorubicin-induced cardiotoxicity. 56 Another area of investigation in which imaging is facilitating understanding relates to predisposing factors such as common polymorphisms in genes involved in anthracycline metabolism.…”

Section: Cardio-oncologymentioning

confidence: 99%

“…El mayor beneficio de avances en imágenes es probable que esté en la evaluación de análogos con menor cardiotoxicidad y con agentes que reducen la cardiotoxicidad o agentes y regímenes quimioterápicos bien establecidos. 54 Ejemplos de esta estrategia incluyen la evaluación de análogos de las antraciclinas que apuntan a la isoenzima Top2α, que puede ser menos cardiotóxica, agentes como el dexrazoxano, 55 y una neuregulina-1β, que reduce la toxicidad en la cardiotoxicidad inducida por doxorubicina. 56 Otra área de investigación en la que las imágenes están facilitando la comprensión se refiere a los factores predisponentes como polimorfismos comunes en los genes implicados en el metabolismo de antraciclinas.…”

Section: Cardio-oncologíaunclassified

The Future of Cardiovascular Imaging

2016

View full text Add to dashboard Cite

O ver the past 2 decades, we have witnessed an explosive expansion in the armamentarium of noninvasive and invasive imaging technologies capable of providing detailed information about the structure and function of the heart and vasculature. Many of these technologies are integrative (eg, positron emission tomography and computed tomography, positron emission tomography and MRI), thereby compounding the unique strengths of the component technologies to achieve unprecedented improvements to our ability to diagnose disease, improve patient care, and advance biomedical research. In addition, the miniaturization of imaging devices with dramatic increases in sensitivity and spatial resolution, coupled with the development of quantitative molecular imaging approaches for evaluating physiology and pathobiology at the cellular and molecular levels, provides a unique platform for a new era in diagnostic imaging. The crucial role of imaging in early phenotyping of disease, risk assessment, and management guidance is expanding rapidly in ways previously thought unrealistic.Along with clinical, molecular, and genomewide association studies, structural and functional quantitative imaging already plays a critical role in phenotyping cardiovascular disease. Unique strengths of imaging phenotyping include its ability to provide precise, organ-specific anatomic localization and quantification of disease traits, to demonstrate and quantify involvement of other organs in cardiac disease, to provide an opportunity to investigate the time course of disease-specific molecular events in vivo, and to track their response to therapy. In so doing, quantitative structural and functional imaging can provide a nuanced description of disease burden (eg, atherosclerosis, myocarditis), disease subtypes (eg, amyloidosis), and, importantly, the relationship between the specific phenotype and outcomes, thereby informing treatment strategies and allowing more personalized approaches to patient management.Our objectives for this article are to (1) provide a viewpoint regarding the evolving role of cardiovascular imaging in biomedical research and clinical practice, (2) discuss the challenges associated with clinical translation of imaging innovations and the opportunities for multimodality imaging in the changing paradigm of value-based medicine, and (3) briefly outline future challenges and opportunities including the requirements for training future generations of imaging scientists and clinical specialists. Unlike traditional reviews that provide a detailed discussion of the role of 1 or more imaging modalities in cardiovascular (CV) disease, our discussion will focus on the potential role of imaging in what we believe are key areas of the translational highway with specific examples on how structural and functional imaging may contribute to scientific discovery, diagnosis, risk stratification, and patient management in each of those areas. Redefining the Role of Imaging Across the Continuum of Biomedical Research and Clinical Practice Translati...

show abstract

Early and delayed cardioprotective intervention with dexrazoxane each show different potential for prevention of chronic anthracycline cardiotoxicity in rabbits

Cited by 30 publications

References 43 publications

Myocardial Protection During Cardiotoxic Chemotherapy

Myocardial Protection During Cardiotoxic Chemotherapy

Dexrazoxane exacerbates doxorubicin-induced testicular toxicity

The Future of Cardiovascular Imaging

Contact Info

Product

Resources

About