Propofol attenuation of hydrogen peroxide-mediated oxidative stress and apoptosis in cultured cardiomyocytes involves haeme oxygenase-1.
OBJECTIVE
Our aim was to investigate the cytoprotective effect of propofol against hydrogen peroxide (H2O2)-mediated injury and the effects on the haeme oxygenase-1 system, which is a possible new cytoprotective pathway of propofol.


METHODS
Primary cultured newborn rat cardiomyocytes were divided into five groups: (1) untreated (Group control); (2) treated with 200 micromol L(-1) H2O2 (Group H) and treated with 200 micromol L(-1) H2O2 in the presence of propofol (25, 50 and 100 micromol L(-1), (3) Group 25P + H, (4) Group 50P + H and (5) Group 100P + H, respectively); added with zinc protoporphyrin IX (ZnPPIX) (10 micromol L(-1)), a potent inhibitor of haeme oxygenase activity, or SC-3060 (0.2 micromol L(-1)), a specific synthetic inhibitor of nuclear factor kappaB. All were incubated for 6 h. The protective effects of propofol were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide cytotoxicity assay, the concentration of malondialdehyde, superoxide dismutase activity and cell apoptosis by enzyme-linked immunosorbent assay (ELISA). Reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis were used to detect haeme oxygenase-1 expression.


RESULTS
Compared with H2O2, propofol concentrations (ranging from 50 to 100 micromol L(-1)) significantly increased haeme oxygenase-1 expression and decreased cardiomyocytes apoptosis, accompanied with a decrease in malondialdehyde, but with an increase in superoxide dismutase activity and cell activity (P < 0.05 and P < 0.01, respectively). The protective effects of propofol were mitigated by the addition of ZnPPIX. The addition of SC-3060 reversed propofol-induced haeme oxygenase-1 expression.


CONCLUSIONS
Propofol can protect cardiomyocytes against H2O2-mediated cytotoxicity in a dose-dependent manner and increase haeme oxygenase-1 expression, which may partly mediate the cytoprotective effects of propofol.
Xu
J-J
JJ
Renmin Hospital of Wuhan University, Department of Anesthesiology, Anesthesiology Research Laboratory, Wuhan, PR China. jjxsabrina@163.com
Wang
Y-L
YL
D000704:Analysis of Variance; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008315:Malondialdehyde / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
D018686:Anesthetics, Intravenous; D004791:Enzyme Inhibitors; D016877:Oxidants; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D015742:Propofol