We have located links that may give you full text access.
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 2018 April
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.
Full text links
Related Resources
Trending Papers
Heart failure with preserved ejection fraction: diagnosis, risk assessment, and treatment.Clinical Research in Cardiology : Official Journal of the German Cardiac Society 2024 April 12
Proximal versus distal diuretics in congestive heart failure.Nephrology, Dialysis, Transplantation 2024 Februrary 30
Efficacy and safety of pharmacotherapy in chronic insomnia: A review of clinical guidelines and case reports.Mental Health Clinician 2023 October
World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management.American Journal of Hematology 2024 March 30
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app