Propofol ameliorates doxorubicin-induced oxidative stress and cellular apoptosis in rat cardiomyocytes.
Toxicol Appl Pharmacol
; 257(3): 437-48, 2011 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-22015447
ABSTRACT
BACKGROUND:
Propofol is an anesthetic with pluripotent cytoprotective properties against various extrinsic insults. This study was designed to examine whether this agent could also ameliorate the infamous toxicity of doxorubicin, a widely-used chemotherapeutic agent against a variety of cancer diseases, on myocardial cells.METHODS:
Cultured neonatal rat cardiomyocytes were administrated with vehicle, doxorubicin (1µM), propofol (1µM), or propofol plus doxorubicin (given 1h post propofol). After 24h, cells were harvested and specific analyses regarding oxidative/nitrative stress and cellular apoptosis were conducted.RESULTS:
Trypan blue exclusion and MTT assays disclosed that viability of cardiomyocytes was significantly reduced by doxorubicin. Contents of reactive oxygen and nitrogen species were increased and antioxidant enzymes SOD1, SOD2, and GPx were decreased in these doxorubicin-treated cells. Mitochondrial dehydrogenase activity and membrane potential were also depressed, along with activation of key effectors downstream of mitochondrion-dependent apoptotic signaling. Besides, abundance of p53 was elevated and cleavage of PKC-δ was induced in these myocardial cells. In contrast, all of the above oxidative, nitrative and pro-apoptotic events could be suppressed by propofol pretreatment.CONCLUSIONS:
Propofol could extensively counteract oxidative/nitrative and multiple apoptotic effects of doxorubicin in the heart; hence, this anesthetic may serve as an adjuvant agent to assuage the untoward cardiac effects of doxorubicin in clinical application.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doxorrubicina
/
Propofol
/
Estresse Oxidativo
/
Anestésicos Intravenosos
/
Antibióticos Antineoplásicos
Limite:
Animals
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Taiwan