Preventive effects of fasudil on adriamycin-induced cardiomyopathy: possible involvement of inhibition of RhoA/ROCK pathway.
Food Chem Toxicol
; 49(11): 2975-82, 2011 Nov.
Article
em En
| MEDLINE
| ID: mdl-21803115
ABSTRACT
The aim of this study was to investigate the involvement of the RhoA/Rho kinase (ROCK) signaling pathway in the progression of ADR-induced heart failure. Rats were administered captopril or fasudil over a period of 6 days, and the ADR was injected intraperitoneally on day 4. Similar to the effect of captopril, fasudil treatment significantly protected against ADR-induced hemodynamic, histopathologic and ultra-structural changes and decreased plasma lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) in a dose-dependent manner in the left ventricle of the heart. While ADR treatment induced ROCKI mRNA expression, fasudil significantly and dose-dependently reduced the incidence of apoptosis and the ratio of bax/bcl-2 protein expression. Moreover, a dose-related decrease in c-jun mRNA expression and an increase in c-FLIP (L) expression were observed in the fasudil groups. Fasudil also downregulated NF-κB activity in a dose-dependent manner. These data indicated that the RhoA/ROCK signaling pathway plays an important role in the progression of heart failure induced by ADR, while fasudil increased resistance to cardiac cell injury. The mechanisms of fasudil-mediated protection against ADR-induced apoptosis may be related to higher c-FLIP (L) and bcl-2 expression, lower c-jun expression and inhibition of NF-κB activation in the heart.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doxorrubicina
/
1-(5-Isoquinolinasulfonil)-2-Metilpiperazina
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Proteína rhoA de Ligação ao GTP
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Quinases Associadas a rho
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Cardiomiopatias
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article