About: Early and delayed cardioprotective intervention with dexrazoxane each show different potential for prevention of chronic anthracycline cardiotoxicity in rabbits     Goto   Sponge   NotDistinct   Permalink

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  • The aim of this study was to compare early and currently recommended delayed intervention with dexrazoxane (DEX) against chronic anthracycline (ANT) cardiotoxicity on the rabbit model - i.e. administration of DEX with each ANT dose or since cumulative dose 300 mg/m2 of ANT, respectively, and to investigate molecular mechanisms involved in this matter. We found that both DEX dosing schedules prevented ANT-induced premature deaths and severe congestive heart failure, but only the early intervention completely prevented the left ventricular dysfunction, myocardial morphological changes, mitochondrial damage and ANT-induced down-regulation of expression of mitochondrial proteins encoded by both nuclear and mitochondrial genome. Further molecular analyses did not support the assumption that DEX cardioprotection is based and directly proportional to protection from ANT-induced oxidative damage and/or deletions in mtDNA. Hence, the present functional, morphological as well as the molecular data highlight the enormous cardioprotective effects of DEX and provide novel insights into the molecular events involved. Furthermore, the data suggests that currently recommended delayed intervention may not be able to take advantage of the full cardioprotective potential of the drug and thus, it deserves further discussion and potential reconsideration.
  • The aim of this study was to compare early and currently recommended delayed intervention with dexrazoxane (DEX) against chronic anthracycline (ANT) cardiotoxicity on the rabbit model - i.e. administration of DEX with each ANT dose or since cumulative dose 300 mg/m2 of ANT, respectively, and to investigate molecular mechanisms involved in this matter. We found that both DEX dosing schedules prevented ANT-induced premature deaths and severe congestive heart failure, but only the early intervention completely prevented the left ventricular dysfunction, myocardial morphological changes, mitochondrial damage and ANT-induced down-regulation of expression of mitochondrial proteins encoded by both nuclear and mitochondrial genome. Further molecular analyses did not support the assumption that DEX cardioprotection is based and directly proportional to protection from ANT-induced oxidative damage and/or deletions in mtDNA. Hence, the present functional, morphological as well as the molecular data highlight the enormous cardioprotective effects of DEX and provide novel insights into the molecular events involved. Furthermore, the data suggests that currently recommended delayed intervention may not be able to take advantage of the full cardioprotective potential of the drug and thus, it deserves further discussion and potential reconsideration. (en)
Title
  • Early and delayed cardioprotective intervention with dexrazoxane each show different potential for prevention of chronic anthracycline cardiotoxicity in rabbits
  • Early and delayed cardioprotective intervention with dexrazoxane each show different potential for prevention of chronic anthracycline cardiotoxicity in rabbits (en)
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  • Early and delayed cardioprotective intervention with dexrazoxane each show different potential for prevention of chronic anthracycline cardiotoxicity in rabbits
  • Early and delayed cardioprotective intervention with dexrazoxane each show different potential for prevention of chronic anthracycline cardiotoxicity in rabbits (en)
skos:notation
  • RIV/00216208:11160/13:10139301!RIV14-GA0-11160___
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • I, P(GA13-15008S)
http://linked.open...iv/cisloPeriodika
  • 3
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
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  • 71047
http://linked.open...ai/riv/idVysledku
  • RIV/00216208:11160/13:10139301
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  • mechanisms; heart failure; cardiotoxicity; anthracycline; cardioprotection; dexrazoxane (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • NL - Nizozemsko
http://linked.open...ontrolniKodProRIV
  • [E619FB7BEA02]
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  • Toxicology
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http://linked.open...ichTvurcuVysledku
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http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 311
http://linked.open...iv/tvurceVysledku
  • Adamcová, Michaela
  • Mičuda, Stanislav
  • Šimůnek, Tomáš
  • Geršl, Vladimír
  • Jirkovský, Eduard
  • Štěrba, Martin
  • Hroch, Miloš
  • Mazurová, Yvona
  • Vávrová, Jaroslava
  • Lenčová-Popelová, Olga
http://linked.open...ain/vavai/riv/wos
  • 000324609200013
issn
  • 0300-483X
number of pages
http://bibframe.org/vocab/doi
  • 10.1016/j.tox.2013.06.012
http://localhost/t...ganizacniJednotka
  • 11160
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