Effects of propofol on hypoxia/reoxygenation induced neuronal cell damage in vitro.
Background: Propofol, a widely used intravenous anaesthetic agent, has been shown to protect neuronal cells from hypoxia/reoxygenation injury. However, the underlying mechanisms of these neuroprotective effects are still unclear but may be related to reactive oxygen species which are produced during hypoxia/reoxygenation induced injury. Aim of the study was to investigate the molecular and cellular effects of propofol on hypoxia-induced cell-damage employing the neuronal cell line IMR-32. Results: Hypoxia led to morphological signs of cell damage and increased the release of LDH (hypoxia: 0.78±0.21 a.u., normoxia: 0.39±0.07 a.u.; P<0.05). Addition of propofol significantly reduced the hypoxia induced LDH release (hypoxia + propofol: 0.44±0.17 a.u.; P<0.05 vs hypoxia), diminished morphological signs of cell damage but did not influence protein levels of caspase-3. Reactive oxygen species were increased under hypoxic conditions and significantly reduced by the addition of propofol (hypoxia: 267.70±28.91 a.u., normoxia: 206.60±27.99 a.u.; P<0.01; hypoxia + propofol: 234.00±33.39 a.u.; P<0.05 vs hypoxia). Addition of propofol also decreased hydrogen peroxide levels (hypoxia: 17.38±2.70 μM, hypoxia + propofol: 13.22±1.29 μM; P<0.05). Western blotting experiments showed increased amounts of catalase under hypoxic conditions (hypoxia: 1.29±0.04 a.u., normoxia: 0.92±0.04 a.u.; P<0.001). Addition of propofol decreased the amount of catalase (hypoxia + propofol: 1.04±0.03 a.u.; P<0.01 vs hypoxia) but increased enzymatic activity of the protein (hypoxia: 2.45±0.46 U/ml, hypoxia + propofol 5.17±1.68 U/ml; P<0.05). Conclusion: We suggest that propofol protects neuronal cells from hypoxia/reoxygenation injury and that the associated events may besides direct antioxidant actions of propofol also be due to the capability of the anaesthetic to induce cellular antioxidant mechanisms.