Propofol ameliorates doxorubicin-induced oxidative stress and cellular apoptosis in rat cardiomyocytes.
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.
Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan.
H C
HC
Lai
Y C
YC
Yeh
L C
LC
Wang
C T
CT
Ting
W L
WL
Lee
H W
HW
Lee
K Y
KY
Wang
A
A
Wu
C S
CS
Su
T J
TJ
Liu
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004317:Doxorubicin / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D018686:Anesthetics, Intravenous; D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D004317:Doxorubicin; D015742:Propofol