BACKGROUND: Cardiac toxicity associated with chronic administration of anthracycline (ANT) antibiotics represents a serious complication of their use in anticancer chemotherapy, but can also serve as a useful experimental model of cardiomyopathy and congestive heart failure. AIMS: In this study, a model of chronic ANT cardiotoxicity induced by repeated i.v. daunorubicin (DAU) administration to rabbits was tested. METHODS: Three groups of animals were used: (1) control group-10 animals received i.v. saline; (2) 11 animals received DAU (3 mg/kg, i.v.); (3) 5 animals received the model cardioprotective agent dexrazoxane (DEX, 60 mg/kg, i.p.), 30 min prior to DAU. All substances were administered once weekly, for 10 weeks. The DAU-induced heart damage and protective action of DEX were determined and quantitated with the use of histopathology, invasive haemodynamic measurements (e.g. left ventricular pressure changes-dP/dt(max), dP/dt(min)), non-invasive systolic function examinations (left ventricular ejection fraction, PEP/LVET index) and biochemical analysis of cardiac troponin T plasma concentrations. RESULTS: All the employed methods showed unambiguously pronounced heart impairment in the DAU group, with the development of both systolic and diastolic heart failure, as well as significant reduction of DAU-cardiotoxicity in DEX-pretreated animals. Other toxicities were acceptable. CONCLUSION: The presented model has been approved to be consistent and reliable and it can serve as a basis for future determinations and comparisons of chronic cardiotoxic effects of various drugs, as well as for the evaluation of potential cardioprotectants.

Department of Pharmacology and Toxicology Faculty of Pharmacy in Hradec Králové Charles University Prague Heyrovského 1203 500 05 Hradec Králové Czech Republic

Komentář v

Eur J Heart Fail. 2004 Jun;6(4):375-6. doi: 10.1016/j.ejheart.2003.12.017. PubMed

Citace poskytuje Crossref.org

Topobexin targets the Topoisomerase II ATPase domain for beta isoform-selective inhibition and anthracycline cardioprotection

Exploring the effects of topoisomerase II inhibitor XK469 on anthracycline cardiotoxicity and DNA damage

Development of water-soluble prodrugs of the bisdioxopiperazine topoisomerase IIβ inhibitor ICRF-193 as potential cardioprotective agents against anthracycline cardiotoxicity

Cardiac Troponins are Among Targets of Doxorubicin-Induced Cardiotoxicity in hiPCS-CMs

Molecular remodeling of left and right ventricular myocardium in chronic anthracycline cardiotoxicity and post-treatment follow up

Oxidative stress, redox signaling, and metal chelation in anthracycline cardiotoxicity and pharmacological cardioprotection

Dexrazoxane-afforded protection against chronic anthracycline cardiotoxicity in vivo: effective rescue of cardiomyocytes from apoptotic cell death