Background
Anesthetic isoflurane has been reported to induce caspase-3 activation. The underlying mechanism(s) and targeted intervention(s), however, remain largely to be determined. Vitamin C (VitC) inhibits oxidative stress and apoptosis. We therefore employed VitC to further determine the up-stream mechanisms and the down-stream consequences of the isoflurane-induced caspase-3 activation.
Methods
H4 human neuroglioma cells over expressed human amyloid precursor protein (H4-APP cells) and rat neuroblastoma cells were treated either with: 1) 2% isoflurane or 2) the control condition, plus saline or 400 mM VitC for three or six hours. Western blot analysis and fluorescence assay was utilized at the end of the experiments to determine caspase-3 activation, levels of reactive oxygen species and ATP, and mitochondrial function. The interaction of isoflurane (1.4% for two hours) and VitC (80 mg/kg) on cognitive function in mice was also assessed in the Fear Conditioning System.
Results
Here we show for the first time that the VitC treatment attenuated the isoflurane-induced caspase-3 activation. Moreover, VitC mitigated the isoflurane-induced increase in the levels of reactive oxygen species, opening of mitochondrial permeability transition pore, reduction in mitochondrial membrane potential, and the reduction in ATP levels in the cells. Finally, VitC ameliorated the isoflurane-induced cognitive impairment in the mice.
Conclusion
Pending confirmation from future studies, these results suggested that VitC attenuated the isoflurane-induced caspase-3 activation and cognitive impairment by inhibiting the isoflurane-induced oxidative stress, mitochondrial dysfunction, and reduction in ATP levels. These findings would promote further research into the underlying mechanisms and targeted interventions of anesthesia neurotoxicity.