The Effects of Sodium Dichloroacetate on Mitochondrial Dysfunction and Neuronal Death Following Hypoglycemia-Induced Injury
AbstractOur previous studies demonstrated that some degree of neuronal death is caused by hypoglycemia, but a subsequent and more severe wave of neuronal cell death occurs due to glucose reperfusion, which results from the rapid restoration of low blood glucose levels. Mitochondrial dysfunction caused by hypoglycemia leads to increased levels of pyruvate dehydrogenase kinase (PDK) and suppresses the formation of ATP by inhibiting pyruvate dehydrogenase (PDH) activation, which can convert pyruvate into acetyl-coenzyme A (acetyl-CoA). Sodium dichloroacetate (DCA) is a PDK inhibitor and activates PDH, the gatekeeper of glucose oxidation. However, no studies about the effect of DCA on hypoglycemia have been published. In the present study, we hypothesized that DCA treatment could reduce neuronal death through improvement of glycolysis and prevention of reactive oxygen species production after hypoglycemia. To test this, we used an animal model of insulin-induced hypoglycemia and injected DCA (100 mg/kg, i.v., two days) following hypoglycemic insult. Histological evaluation was performed one week after hypoglycemia. DCA treatment reduced hypoglycemia-induced oxidative stress, microglial activation, blood–brain barrier disruption, and neuronal death compared to the vehicle-treated hypoglycemia group. Therefore, our findings suggest that DCA may have the therapeutic potential to reduce hippocampal neuronal death after hypoglycemia. View Full-Text
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Kho, A.R.; Choi, B.Y.; Lee, S.H.; Hong, D.K.; Jeong, J.H.; Kang, B.S.; Kang, D.H.; Park, K.-H.; Park, J.B.; Suh, S.W. The Effects of Sodium Dichloroacetate on Mitochondrial Dysfunction and Neuronal Death Following Hypoglycemia-Induced Injury. Cells 2019, 8, 405.
Kho AR, Choi BY, Lee SH, Hong DK, Jeong JH, Kang BS, Kang DH, Park K-H, Park JB, Suh SW. The Effects of Sodium Dichloroacetate on Mitochondrial Dysfunction and Neuronal Death Following Hypoglycemia-Induced Injury. Cells. 2019; 8(5):405.Chicago/Turabian Style
Kho, A R.; Choi, Bo Y.; Lee, Song H.; Hong, Dae K.; Jeong, Jeong H.; Kang, Beom S.; Kang, Dong H.; Park, Kyoung-Ha; Park, Jae B.; Suh, Sang W. 2019. "The Effects of Sodium Dichloroacetate on Mitochondrial Dysfunction and Neuronal Death Following Hypoglycemia-Induced Injury." Cells 8, no. 5: 405.
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