ABSTRACT Anthracycline-based antineoplastic therapy is the standard of care for various cancers today and represents a breakthrough in this area. The cardiac toxicity of anthracyclines is well established. The acute form is often reversible and has no predictive value for the future. This early form does not prevent continuation of chemotherapy. Late cardiac toxicity due to anthracycline is the leading limiting factor in its use. In adults, this resembles dilated cardiomyopathy, while in children it may be expressed as restrictive cardiomyopathy. The discovery of modifiable risk factors has made it possible to identify patients at high risk of developing late cardiac toxicity and heart failure. Because left ventricular dysfunction and heart failure may develop long after anthracycline treatment ends, prolonged close follow-up is mandatory in asymptomatic subjects. Follow-up of asymptomatic patients requires serial echocardiography (M-mode, 2D echo, Doppler, tissue Doppler, speckle tracking, etc.). Anthracycline-induced cardiomyopathy must be treated according to the standard guidelines for chronic heart failure with left ventricular dysfunction, by angiotensin-converting enzyme (ACE) inhibitors and beta-blockers. Lifestyle changes may reduce the long-term risk. Close collaboration between cardiologists and oncologists is highly desirable for optimizing management of these patients.
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ABSTRACT: Doxorubicin (DOXO) is an anthracycline antibiotic which is used in the treatment of human malignancies such as leukemia, lymphoma and a number of solid tumors, particularly breast cancer. Anthracyclines have been reported to contaminate chemotherapy workstation surfaces as well as other workplaces surfaces. The occupational exposure to these drugs could occur in hospitals, for nurses involved in anthracyclines preparation and administration, in chemical industries during the commercial formulate syntheses, and in analytical laboratories. Numerous studies investigated cutaneous effects related to DOXO administration, on the contrary few literature data are available about effects on the skin due to the direct contact with the drug. The present study investigated the DOXO permeability of three commercially available gloves' types used to protect skin in occupational contexts, as well as the effects of DOXO on human keratinocyte cell line (HaCaT). The results suggest that the DOXO permeability of gloves depends not only on glove material but also on DOXO solutions' pH, in fact nitrile gloves can be penetrated by acid solutions, while neither natural rubbers nor nitrile gloves are permeable to neutral solutions. Moreover, DOXO solutions, even at low concentration, cause apoptosis in epithelial cells, through activation of intrinsic pathway p53-independent.Toxicology Letters 05/2010; 197(2):61-8. DOI:10.1016/j.toxlet.2010.04.026 · 3.36 Impact Factor
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ABSTRACT: Doxorubicin, a widely used chemotherapeutic agent, can give rise to severe cardiotoxicity by inducing cardiomyocyte apoptosis. Dracocephalum rupestre Hance, a Chinese traditional herb, has therapeutic potential for cardiovascular diseases. Naringenin-7-O-glucoside is the main active constituent of D. rupestre and there is increasing interest in its therapeutic applications. The aim of this study was to evaluate the effects of naringenin-7-O-glucoside on cardiomyocyte apoptosis induced by doxorubicin. Cell viability was detected by MTT assay. Naringenin-7-O-glucoside (10, 20, and 40 microM) significantly enhanced cardiomyocyte proliferation relative to that of doxorubicin. Furthermore, naringenin-7-O-glucoside increased the protein levels of heme oxygenase-1 (HO-1) and Bcl-2 in cardiomyocytes (as detected by Western blotting) and suppressed the mRNA expression of caspase-3 and caspase-9 (as detected by RT-PCR). These results suggest that naringenin-7-O-glucoside has protective effects against doxorubicin-induced apoptosis, effects which could underlie the use of naringenin-7-O-glucoside therapeutic agent for treating or preventing cardiomyopathy associated with doxorubicin.European Journal of Pharmacology 03/2008; 581(1-2):47-53. DOI:10.1016/j.ejphar.2007.11.048 · 2.68 Impact Factor
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ABSTRACT: The clinical use of doxorubicin (DOX) and other anthracyclines is limited by a dosage-dependent cardiotoxicity, which can lead to cardiomyopathy. The role of the individual genetic makeup in this disorder is poorly understood. Alterations in genes encoding cardiac cytoskeleton or sarcolemma proteins may increase the susceptibility to doxorubicin-related cardiotoxicity. Female dystrophin-deficient mice (MDX) and age-matched wild-type mice underwent chronic treatment with doxorubicin. Cardiac function and tissue damage were assessed by echocardiography and histopathology, respectively. Gene expression changes were investigated using microarrays. DOX treatment resulted in mortality, cardiac insufficiency, and cardiac interstitial fibrosis. These alterations were more pronounced in DOX-treated MDX mice than in DOX-treated wild-type mice. Changes in gene expression were more numerous in MDX mice, including genes involved in cell adhesion, oxidative stress, cytoskeleton organization, inflammatory and immune response and cell death. Dystrophin deficiency facilitates the development and progression of doxorubicin-induced cardiac injury. The underlying mechanisms may involve changes in cell adhesion, in cytoskeleton, as well as in inflammatory and immune responses. Genetic variants of cytoskeletal proteins in humans may affect the individual susceptibility to doxorubicin. Cardiotoxic drugs may accelerate the manifestation of pre-clinical cardiomyopathies caused by deficiencies in cytoskeletal or sarcolemma proteins.European Journal of Heart Failure 11/2007; 9(10):986-94. DOI:10.1016/j.ejheart.2007.07.016 · 6.58 Impact Factor