2-Deoxy-D-Glucose Enhances Anesthetic Effects in Mice. (February 2015)

• Record Type: Journal Article
• Authors: Wang, Hui; Xu, Zhipeng; Wu, Anshi; Dong, Yuanlin; Zhang, Yiying; Yue, Yun; Xie, Zhongcong
• Is Part Of: Anesthesia & analgesia. Volume 120:Number 2(2015)
• Publication Date: 2015-02
• Subjects: Anesthesiology -- Periodicals; Anesthesia; Anesthesiology; Analgesia; Analgesics; Anesthesiology -- Periodicals; 617.9605
• DOI: 10.1213/ANE.0000000000000520
• Languages: English
• ISSNs: 0003-2999

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>BACKGROUND:</title> <p>The mechanisms of general anesthesia by volatile drugs remain largely unknown. Mitochondrial dysfunction and reduction in energy levels have been suggested to be associated with general anesthesia status. 2-Deoxy-D-glucose (2-DG), an analog of glucose, inhibits hexokinase and reduces cellular levels of adenosine triphosphate (ATP). 3-Nitropropionic acid is another compound which can deplete ATP levels. In contrast, idebenone and L-carnitine could rescue deficits of energy. We therefore sought to determine whether 2-DG and/or 3-nitropropionic acid can enhance the anesthetic effects of isoflurane, and whether idebenone and L-carnitine can reverse the actions of 2-DG.</p> </sec> <sec> <title>METHODS:</title> <p>C57BL/6J mice (8 months old) received different concentrations of isoflurane with and without the treatments of 2-DG, 3-nitropropionic acid, idebenone, and L-carnitine. Isoflurane-induced loss of righting reflex (LORR) was determined in the mice. ATP levels in H4 human neuroglioma cells were assessed after these treatments. Finally, 31P-magnetic resonance spectroscopy was used to determine the effects of isoflurane on brain ATP levels in the mice.</p> </sec> <sec> <title>RESULTS:</title> <p>2-DG enhanced isoflurane-induced LORR (<italic>P</italic> = 0.002, <italic>N</italic> = 15). 3-Nitropropionic acid also enhanced the anesthetic effects of isoflurane (<italic>P</italic> = 0.005, <italic>N</italic> = 15). Idebenone (idebenone + saline versus idebenone + 2-DG: <italic>P</italic> = 0.165, <italic>N</italic> = 15), but not L-carnitine (L-carnitine + saline versus L-carnitine + 2-DG: <italic>P</italic> < 0.0001, <italic>N</italic> = 15), inhibited the effects of 2-DG on enhancing isoflurane-induced LORR in the mice, as evidenced by 2-DG not enhancing isoflurane-induced LORR in the mice pretreated with idebenone. Idebenone (idebenone + saline versus idebenone + 2-DG: <italic>P</italic> = 0.177, <italic>N</italic> = 6), but not L-carnitine (L-carnitine + saline versus L-carnitine + 2-DG: <italic>P</italic> = 0.029, <italic>N</italic> = 6), also mitigated the effects of 2-DG on reducing ATP levels in cells, as evidenced by 2-DG not decreasing ATP levels in the cells pretreated with idebenone. Finally, isoflurane decreased ATP levels in both cultured cells and mouse brains (β-ATP: <italic>P</italic> = 0.003, <italic>N</italic> = 10; β-ATP/phosphocreatine: <italic>P</italic> = 0.006, <italic>N</italic> = 10; β-ATP/inorganic phosphate: <italic>P</italic> = 0.001, <italic>N</italic> = 10).</p> </sec> <sec> <title>CONCLUSIONS:</title> <p>These results from our pilot studies have established a system and generated a hypothesis that 2-DG enhances anesthetic effects via reducing energy levels. These findings should promote further studies to investigate anesthesia mechanisms.</p> </sec> </abstract>