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The Effects of Hispidulin on Bupivacaine-Induced Neurotoxicity: Role of AMPK Signaling Pathway

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Abstract

Bupivacaine is a sodium channel blocker, which is widely used for local infiltration nerve block, epidural and intrathecal anesthesia. However, bupivacaine could cause nerve damage. Hispidulin was shown to be able to penetrate the blood–brain barrier and possess antiepileptic activity. In this study, we investigate whether hispidulin administration could attenuate bupivacaine-induced neurotoxicity. Bupivacaine-challenged mouse neuroblastoma N2a cells were treated with hispidulin. The neuron injury was assessed by examination of cell viability and apoptosis. The levels of activation of AMP-activated protein kinase (AMPK) signaling pathway were examined along with the effect of blocking AMPK signaling on cell viability in the presence of hispidulin and bupivacaine. Our results showed that Bupivacaine treatment significantly decreased cell viability and induced apoptosis. Treatment with hispidulin significantly attenuated bupivacaine-induced cell injury. In addition, hispidulin treatment increased the levels of phospho-AMPK and phospho-GSK3β and attenuated bupivacaine-induced loss in mitochondrial membrane potential. Furthermore, we found that blocking AMPK signaling pathway significantly abolished the cytoprotective effect of hispidulin against bupivacaine-induced cell injury. Our findings suggest that treatment of neuroblastoma cells with hispidulin-protected neural cells from Bupivacaine-induced injury via the activation of the AMPK/GSK3β signaling pathway.

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Authors and Affiliations

  1. Department of Anesthesiology, Shandong Provincial Hospital, Shandong University, No.324, JingWu Road, Jinan, 250021, China

    Xinhuan Niu, Ping Wang, Hui Zhou, Song Li & Mengyuan Zhang

  2. Department of General Surgery, People’s Hospital of Huai Yin District, Jinan, 250021, China

    Jie Chen

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  1. Xinhuan Niu
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  2. Jie Chen
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  3. Ping Wang
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  4. Hui Zhou
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  5. Song Li
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  6. Mengyuan Zhang
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Correspondence to Mengyuan Zhang.

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Xinhuan Niu and Jie Chen have contributed equally to this work.

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Niu, X., Chen, J., Wang, P. et al. The Effects of Hispidulin on Bupivacaine-Induced Neurotoxicity: Role of AMPK Signaling Pathway. Cell Biochem Biophys 70, 241–249 (2014). https://doi.org/10.1007/s12013-014-9888-5

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