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Preventive effects of fasudil on adriamycin-induced cardiomyopathy: Possible involvement of inhibition of RhoA/ROCK pathway
- Source :
-
Food & Chemical Toxicology . Nov2011, Vol. 49 Issue 11, p2975-2982. 8p. - Publication Year :
- 2011
-
Abstract
- 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 6days, 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 ROCK I 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. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 02786915
- Volume :
- 49
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Food & Chemical Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 66412489
- Full Text :
- https://doi.org/10.1016/j.fct.2011.06.080