RGD Reference Report - New developments in anthracycline-induced cardiotoxicity. - Rat Genome Database

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New developments in anthracycline-induced cardiotoxicity.

Authors: Mordente, A  Meucci, E  Silvestrini, A  Martorana, GE  Giardina, B 
Citation: Mordente A, etal., Curr Med Chem. 2009;16(13):1656-72.
RGD ID: 10395262
Pubmed: PMID:19442138   (View Abstract at PubMed)

Anthracyclines are among the most effective anticancer drugs ever developed. Unfortunately, their clinical use is severely limited by the development of a progressive dose-dependent cardiomyopathy that irreversibly evolves toward congestive heart failure, usually refractory to conventional therapy. The pathophysiology of anthracycline-induced cardiomyopathy remains controversial and incompletely understood. The current thinking is that anthracyclines are toxic per se but gain further cardiotoxicity after one-electron reduction with ROS overproduction or two-electron reduction with conversion to C-13 alcohol metabolites. ROS overproduction can probably be held responsible for anthracycline acute cardiotoxicity, but not for all the aspects of progressive cardiomyopathy. Intramyocardial formation of secondary alcohol metabolites might play a key role in promoting the progression of cardiotoxicity toward end-stage cardiomyopathy and congestive heart failure. In this review we also discuss recent developments in: a) the molecular mechanisms underlying anthracycline-induced cardiotoxicity; b) the role of cytosolic NADPH-dependent reductases in anthracycline metabolism; c) the influence of genetic polymorphisms on cardiotoxicity outcome; d) the perspectives on the most promising strategies for limiting or preventing anthracycline-induced cardiotoxicity, focusing on controversial aspects and on recent data regarding analogues of the natural compounds, tumor-targeted formulations and cardioprotective agents.



Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Objects Annotated

Genes (Rattus norvegicus)
Akr1a1  (aldo-keto reductase family 1 member A1)
Cbr1  (carbonyl reductase 1)
Cbr3  (carbonyl reductase 3)
Nos3  (nitric oxide synthase 3)
Nqo1  (NAD(P)H quinone dehydrogenase 1)
Xdh  (xanthine dehydrogenase)

Genes (Mus musculus)
Akr1a1  (aldo-keto reductase family 1, member A1)
Cbr1  (carbonyl reductase 1)
Cbr3  (carbonyl reductase 3)
Nos3  (nitric oxide synthase 3, endothelial cell)
Nqo1  (NAD(P)H dehydrogenase, quinone 1)
Xdh  (xanthine dehydrogenase)

Genes (Homo sapiens)
AKR1A1  (aldo-keto reductase family 1 member A1)
CBR1  (carbonyl reductase 1)
CBR3  (carbonyl reductase 3)
NOS3  (nitric oxide synthase 3)
NQO1  (NAD(P)H quinone dehydrogenase 1)
XDH  (xanthine dehydrogenase)


Additional Information