J-J Xu1, Y-L Wang. 1. Renmin Hospital of Wuhan University, Department of Anesthesiology, Anesthesiology Research Laboratory, Wuhan, PR China. jjxsabrina@163.com
Abstract
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 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. 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.
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 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. 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.
Authors: Baohua Wang; Jayant Shravah; Honglin Luo; Koen Raedschelders; David D Y Chen; David M Ansley Journal: Biochem Biophys Res Commun Date: 2009-08-22 Impact factor: 3.575