Cardioprotective effects of inorganic nitrate/nitrite in chronic anthracycline cardiotoxicity: Comparison with dexrazoxane

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11150%2F16%3A10314970" target="_blank" >RIV/00216208:11150/16:10314970 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11160/16:10314970

Result on the web

<a href="http://www.sciencedirect.com/science/article/pii/S0022282815301590" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0022282815301590</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.yjmcc.2015.12.021" target="_blank" >10.1016/j.yjmcc.2015.12.021</a>

Result language

angličtina

Original language name

Cardioprotective effects of inorganic nitrate/nitrite in chronic anthracycline cardiotoxicity: Comparison with dexrazoxane

Original language description

Dexrazoxane (DEX) is a clinically available cardioprotectant that reduces the toxicity induced by anthracycline (ANT) anticancer drugs; however, DEX is seldom used and its action is poorly understood. Inorganic nitrate/nitrite has shown promising results in myocardial ischemia-reperfusion injury and recently in acute high-dose ANT cardiotoxicity. However, the utility of this approach for overcoming clinically more relevant chronic forms of cardiotoxicity remains elusive. Hence, in this study, the protective potential of inorganic nitrate and nitrite against chronic ANT cardiotoxicity was investigated, and the results were compared to those using DEX. Chronic cardiotoxicity was induced in rabbits with daunorubicin (DAU). Sodium nitrate (1 g/L) was administered daily in drinking water, while sodium nitrite (0.15 or 5 mg/kg) or DEX (60 mg/kg) was administered parenterally before each DAU dose. Although oral nitrate induced a marked increase in plasma NOx, it showed no improvement in DAU-induced mortality, myocardial damage or heart failure. Instead, the higher nitrite dose reduced the incidence of end-stage cardiotoxicity, prevented related premature deaths and significantly ameliorated several molecular and cellular perturbations induced by DAU, particularly those concerning mitochondria. The latter result was also confirmed in vitro. Nevertheless, inorganic nitrite failed to prevent DAU-induced cardiac dysfunction and molecular remodeling in vivo and failed to overcome the cytotoxicity of DAU to cardiomyocytes in vitro. In contrast, DEX completely prevented all of the investigated molecular, cellular and functional perturbations that were induced by DAU. Our data suggest that the difference in cardioprotective efficacy between DEX and inorganic nitrite may be related to their different abilities to address a recently proposed upstream target for ANT in the heart - topoisomerase II beta.

Czech name

—

Czech description

—

Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FR - Pharmacology and apothecary chemistry

OECD FORD branch

—

Project

<a href="/en/project/NT13457" target="_blank" >NT13457: Anthracycline cardiotoxicity – new possibilities of pharmacological cardioprotection and risks of combination with biological targeted anticancer treatment</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Molecular and Cellular Cardiology

ISSN

0022-2828

e-ISSN

—

Volume of the periodical

91

Issue of the periodical within the volume

February

Country of publishing house

GB - UNITED KINGDOM

Number of pages

12

Pages from-to

92-103

UT code for WoS article

000371370300014

EID of the result in the Scopus database

2-s2.0-84953255187