title: Glucose may attenuate isoflurane-induced caspase-3 activation in H4 human neuroglioma cells.
abstract: 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.
authors: From 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.
authors: Yongxing
authors: Y
authors: Sun
authors: Yiying
authors: Y
authors: Zhang
authors: Baiqi
authors: B
authors: Cheng
authors: Yuanlin
authors: Y
authors: Dong
authors: Chuxiong
authors: C
authors: Pan
authors: Tianzuo
authors: T
authors: Li
authors: Zhongcong
authors: Z
authors: Xie
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D018685:Anesthetics, Inhalation / Q000633:toxicity*; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D004789:Enzyme Activation; D005910:Glioma / Q000201:enzymology* / Q000473:pathology; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007530:Isoflurane / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D007530:Isoflurane; C505407:CASP3 protein, human; D053148:Caspase 3; D005947:Glucose