Kardiotoxicita antracyklinových antineoplastických látek a možnosti farmakologické kardioprotekce

• Main Author: Jirkovský, Eduard
• Other Authors: Štěrba, Martin
• Format: Doctoral Thesis
• Language: Czech
• Published: 2013
• Online Access: http://www.nusl.cz/ntk/nusl-328232

- CARDIOTOXICITY OF ANTHRACYCLINE ANTINEOPLASTIC DRUGS AND POSSIBILITIES OF PHARMACOLOGICAL CARDIOPROTECTION Chronic anthracycline (ANT) cardiotoxicity is an important clinical problem which can have a substantial impact on morbidity and mortality of cancer survivors. Dexrazoxane (DEX) is the only agent with clearly evidenced cardioprotective effects in both experimental models and clinical trials. Despite intensive research, precise pathogenesis of chronic ANT cardiotoxicity and molecular mechanisms of cardioprotective effects of DEX remain unknown. Current clinical guidelines recommend not using DEX from the beginning of ANT therapy, but instead only from the cumulative ANT dose of 300 mg /m2. The aim of this work was to study functional, morphological and molecular changes associated with induction of chronic ANT cardiotoxicity and their further development in the post-exposure (follow up) period. Special attention was paid on the role of oxidative stress and possible response of protective antioxidant pathway regulated by Nrf2 as well as on mitochondrial impairment and response of mitochondrial biogenesis pathway. Chronic ANT cardiotoxicity was induced in rabbits by repeated intravenous injections of daunorubicin (DAU, 3 mg/kg, once weekly for 10 weeks). At the end of the treatment, the animals...