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Prevention of hypoglycemia-induced hippocampal neuronal death by N-acetyl-l-cysteine (NAC)

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Abstract

Type 1 and type 2 diabetic patients who are treated with insulin or other blood glucose reducing agents for tight control of blood glucose levels are frequently at risk of experiencing severe hypoglycemia which can lead to seizures, loss of consciousness and death. Hypoglycemic neuronal cell death is not a simple result of low glucose supply to the brain, but, instead, results from a cell death signaling pathway that is started by the re-administration of glucose after glucose deprivation. Zinc is a biologically important element for physiological function of central nervous system. However, excessive zinc release from the presynaptic terminals and subsequent translocation into the postsynaptic neurons may contribute to neuronal death following hypoglycemia. N-acetyl-l-cysteine (NAC) acts as a zinc chelator that alleviates zinc-induced neuronal death processes. In addition, NAC restores levels of neuronal glutathione (GSH), a potent antioxidant, by providing a cell-permeable source of cysteine. Thus, we hypothesized that NAC treatment can reduce neuronal cell death, not only by increasing GSH concentration but also by zinc chelation. As a result, we found that NAC decreased the oxidative stress, zinc release and translocation, and improved the level of glutathione. Therefore, NAC administration alleviated hippocampal neuron death in hypoglycemia-induced rats.

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Acknowledgements

We would like express our special thanks to Dr. Hui Chul Choi (Neurology, Hallym University, College of Medicine, Chuncheon, Korea) for valuable discussions. This work was also supported by Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2016M3C7A1913844) to S.W.S.

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Authors and Affiliations

  1. Department of Physiology, Hallym University, College of Medicine, Chuncheon, Korea

    A Ra Kho, Bo Young Choi, Jin Hee Kim, Song Hee Lee, Dae Ki Hong, Sang Hwon Lee & Sang Won Suh

  2. Department of Nursing, Inha University, Incheon, Korea

    Min Sohn

  3. Department of Neurology, College of Medicine, Hallym University, Chuncheon, Korea

    Jeong Hyun Jeong

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  1. A Ra Kho
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  2. Bo Young Choi
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Correspondence to Sang Won Suh.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the Institutional Animal Studies Care and Use Committee of the Hallym University in Chuncheon, Korea (Protocol # Hallym-2015-50).

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Kho, A.R., Choi, B.Y., Kim, J.H. et al. Prevention of hypoglycemia-induced hippocampal neuronal death by N-acetyl-l-cysteine (NAC). Amino Acids 49, 367–378 (2017). https://doi.org/10.1007/s00726-016-2370-5

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