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Propofol ameliorates doxorubicin-induced oxidative stress and cellular apoptosis in rat cardiomyocytes
- Source :
- Toxicology and Applied Pharmacology. 257:437-448
- Publication Year :
- 2011
- Publisher :
- Elsevier BV, 2011.
-
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 (1 μM), propofol (1 μM), or propofol plus doxorubicin (given 1 h post propofol). After 24 h, 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.
- Subjects :
- Cell Survival
SOD1
SOD2
Apoptosis
Oxidative phosphorylation
Pharmacology
Toxicology
medicine.disease_cause
Antioxidants
Rats, Sprague-Dawley
chemistry.chemical_compound
Animals
Medicine
Myocytes, Cardiac
Doxorubicin
Propofol
Cells, Cultured
Membrane Potential, Mitochondrial
Antibiotics, Antineoplastic
business.industry
Reactive Nitrogen Species
Rats
Oxidative Stress
Animals, Newborn
chemistry
Anesthesia
Trypan blue
Reactive Oxygen Species
business
Anesthetics, Intravenous
Oxidative stress
medicine.drug
Subjects
Details
- ISSN :
- 0041008X
- Volume :
- 257
- Database :
- OpenAIRE
- Journal :
- Toxicology and Applied Pharmacology
- Accession number :
- edsair.doi.dedup.....8396d3d0c49563e8253b976e4e688fd1