Glucose may attenuate isoflurane-induced caspase-3 activation in H4 human neuroglioma cells
Yongxing Sun1, Yiying Zhang, Baiqi Cheng
1From the *Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts; and †Department of Anesthesia, Beijing Tongren Hospital, Capital Medical University, Beijing, P.R. China.
Background:
The commonly used inhaled anesthetic isoflurane has been shown to induce caspase-3 activation. However, the underlying mechanism(s) and targeted intervention(s) remain largely to be determined. Isoflurane may induce caspase-3 activation via causing accumulation of reactive oxygen species (ROS), mitochondrial dysfunction, and reduction in adenosine triphosphate (ATP) levels. Therefore, we performed a hypothesis-generation study to determine whether glucose could attenuate isoflurane-induced caspase-3 activation, ROS accumulation, mitochondrial dysfunction, and ATP reduction in cultured cells.
Methods:
H4 human neuroglioma cells (H4 cells) were treated with 2% isoflurane or the control condition plus saline or 50 mM glucose for 6 or 3 hours. Caspase-3 activation, cell viability, levels of ROS and ATP, and mitochondrial membrane potential were determined at the end of the experiments by Western blot analysis and fluorescence assay.
Results:
We found that the glucose treatment might attenuate isoflurane-induced caspase-3 activation and reduction of cell viability in H4 cells. Moreover, the glucose treatment mitigated the isoflurane-induced increase in ROS levels and reduction in ATP levels in H4 cells. Unexpectedly, we observed that the glucose treatment might not inhibit the isoflurane-induced decrease in mitochondrial membrane potential in H4 cells.
Conclusions:
Pending further studies, these results suggested that glucose might attenuate isoflurane-induced caspase-3 activation through a mitochondria-independent reduction in ROS levels and enhancement in ATP levels. These findings have established a system and suggest that it is worth performing more research to further investigate whether glucose can attenuate anesthesia neurotoxicity.
Insights
Glucose may protect against isoflurane neurotoxicity by reducing reactive oxygen species (ROS) and increasing adenosine triphosphate (ATP) levels, independent of mitochondrial function. Further research is warranted to explore glucose as a neuroprotective agent against anesthesia side effects.
Area of Science:
- Neuroscience
- Anesthesiology
- Cell Biology
Background:
- Inhaled anesthetic isoflurane can activate caspase-3, a key cell death mediator.
- Mechanisms of isoflurane-induced caspase-3 activation, potentially involving reactive oxygen species (ROS), mitochondrial dysfunction, and reduced adenosine triphosphate (ATP), require further elucidation.
- Targeted interventions to mitigate isoflurane's neurotoxic effects are largely undetermined.
Purpose of the Study:
- To investigate whether glucose administration can attenuate isoflurane-induced caspase-3 activation.
- To determine if glucose can prevent isoflurane-induced ROS accumulation, mitochondrial dysfunction, and ATP reduction in cultured cells.
Main Methods:
- H4 human neuroglioma cells were exposed to isoflurane with or without glucose.
- Assays included Western blot for caspase-3 activation and cell viability, and fluorescence assays for ROS, ATP, and mitochondrial membrane potential.
Main Results:
- Glucose treatment attenuated isoflurane-induced caspase-3 activation and reduced cell viability.
- Glucose mitigated isoflurane-induced increases in ROS and reductions in ATP levels.
- Glucose did not inhibit the isoflurane-induced decrease in mitochondrial membrane potential.
Conclusions:
- Glucose may attenuate isoflurane-induced caspase-3 activation via a mitochondria-independent reduction in ROS and enhancement of ATP levels.
- These findings suggest glucose warrants further investigation as a potential intervention against anesthesia-induced neurotoxicity.
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