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Propofol attenuation of hydrogen peroxide-mediated oxidative stress and apoptosis in cultured cardiomyocytes involves haeme oxygenase-1

Published online by Cambridge University Press:  01 May 2008

J.-J. Xu  and
Y.-L. Wang
J.-J. Xu*
Affiliation:
Renmin Hospital of Wuhan University, Department of Anesthesiology, Anesthesiology Research Laboratory, Wuhan, PR China
Y.-L. Wang
Affiliation:
Zhongnan Hospital of Wuhan University, Department of Anesthesiology, Anesthesiology Research Laboratory, Wuhan, PR China
*
Correspondence to: Jin-Jin Xu, Anesthesiology Research Laboratory, Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China. E-mail: [email protected]; Tel: +86 276 390 3016; Fax: +86 278 805 2260
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Summary

Background and 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 μmol L−1 H2O2 (Group H) and treated with 200 μmol L−1 H2O2 in the presence of propofol (25, 50 and 100 μmol L−1, (3) Group 25P + H, (4) Group 50P + H and (5) Group 100P + H, respectively); added with zinc protoporphyrin IX (ZnPPIX) (10 μmol L−1), a potent inhibitor of haeme oxygenase activity, or SC-3060 (0.2 μL mL−1), a specific synthetic inhibitor of nuclear factor κB. 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 μmol 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.

Conclusion

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.

Keywords

ANAESTHETICS INTRAVENOUSPROPOFOLHYDROGEN PEROXIDEHAEME OXYGENASE-1CARDIAC MYOCYTES
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 25 , Issue 5 , May 2008 , pp. 395 - 402
Copyright
Copyright © European Society of Anaesthesiology 2008

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