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Dexmedetomidine impairs P‑glycoprotein‑mediated efflux function in L02 cells via the adenosine 5'‑monophosphate‑activated protein kinase/nuclear factor‑κB pathway

  • Authors:
    • Guo‑Rong He
    • Xiao‑Kun Lin
    • Yong‑Biao Wang
    • Cong‑De Chen

  • View Affiliations

  • Published online on: February 2, 2018     https://doi.org/10.3892/mmr.2018.8549
  • Pages: 5049-5056

  • Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Dexmedetomidine (DEX) a type of the anaesthetic that has been widely used in anaesthesia and intensive care. However, whether DEX affects the pharmacokinetics of drugs remains elusive. As hepatic P‑glycoprotein (P‑gp) serves a critical role in the disposition of drugs, the present study aimed to address whether P‑gp function could be affected by DEX in vitro. In the present study, L02 cells (a normal human liver cell line) were exposed to DEX for 24 h and P‑gp function was evaluated by the intracellular accumulation of Rhodamine 123. The results indicated that P‑gp function was significantly impaired by DEX treatment and that the mRNA levels and protein levels of P‑gp were downregulated in a dose‑ and time‑dependent manner. Importantly, DEX‑induced downregulation of P‑gp was associated with adenosine 5'‑monophosphate-activated protein kinase (AMPK) activation, as it was significantly attenuated by AMPK inhibition using dorsomorphin. Furthermore, the results revealed that changes in the subcellular localisation of nuclear factor (NF)‑κB following AMPK activation were involved in the P‑gp regulation in response to DEX treatment. Collectively, these results suggested that DEX impairs P-glycoprotein‑mediated efflux function in L02 cells via the AMPK/NF‑κB pathway, which provided direct evidence that the hepatic disposition of drugs may be affected by DEX through the downregulation of P‑gp.
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April-2018
Volume 17 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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  • Journal Metrics
  • Impact Factor: 3.4
  • Ranked Medicine Research and Experimental
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  • CiteScore: 6.9
  • CiteScore Rank: Q2: #98/328 Biochemistry, Genetics and Molecular Biology
  • Source Normalized Impact per Paper (SNIP): 0.721
  • SCImago Journal Rank (SJR): 0.65
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Spandidos Publications style
He GR, Lin XK, Wang YB and Chen CD: Dexmedetomidine impairs P‑glycoprotein‑mediated efflux function in L02 cells via the adenosine 5'‑monophosphate‑activated protein kinase/nuclear factor‑κB pathway. Mol Med Rep 17: 5049-5056, 2018
APA
He, G., Lin, X., Wang, Y., & Chen, C. (2018). Dexmedetomidine impairs P‑glycoprotein‑mediated efflux function in L02 cells via the adenosine 5'‑monophosphate‑activated protein kinase/nuclear factor‑κB pathway. Molecular Medicine Reports, 17, 5049-5056. https://doi.org/10.3892/mmr.2018.8549
MLA
He, G., Lin, X., Wang, Y., Chen, C."Dexmedetomidine impairs P‑glycoprotein‑mediated efflux function in L02 cells via the adenosine 5'‑monophosphate‑activated protein kinase/nuclear factor‑κB pathway". Molecular Medicine Reports 17.4 (2018): 5049-5056.
Chicago
He, G., Lin, X., Wang, Y., Chen, C."Dexmedetomidine impairs P‑glycoprotein‑mediated efflux function in L02 cells via the adenosine 5'‑monophosphate‑activated protein kinase/nuclear factor‑κB pathway". Molecular Medicine Reports 17, no. 4 (2018): 5049-5056. https://doi.org/10.3892/mmr.2018.8549