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Pharmaceutics 2018, 10(3), 102; https://doi.org/10.3390/pharmaceutics10030102

Alterations in Expression and Function of ABC Family Transporters at Blood-Brain Barrier under Liver Failure and Their Clinical Significances

Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China
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Received: 27 June 2018 / Revised: 20 July 2018 / Accepted: 21 July 2018 / Published: 23 July 2018
(This article belongs to the Special Issue ABC Transporter-Mediated Drug Disposition)
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Abstract

Liver failure is often associated with hepatic encephalopathy, due to dyshomeostasis of the central nervous system (CNS). Under physiological conditions, the CNS homeostasis is precisely regulated by the blood-brain barrier (BBB). The BBB consists of brain microvessel endothelial cells connected with a junctional complex by the adherens junctions and tight junctions. Its main function is to maintain brain homoeostasis via limiting the entry of drugs/toxins to brain. The brain microvessel endothelial cells are characterized by minimal pinocytotic activity, absent fenestrations, and highly expressions of ATP-binding cassette (ABC) family transporters (such as P-glycoprotein, breast cancer resistance protein and multidrug resistance-associated proteins). These ABC transporters prevent brain from toxin accumulation by pumping toxins out of brain. Accumulating evidences demonstrates that liver failure diseases altered the expression and function of ABC transporters at The BBB, indicating that the alterations subsequently affect drugs’ brain distribution and CNS activity/neurotoxicity. ABC transporters also mediate the transport of endogenous substrates across the BBB, inferring that ABC transporters are also implicated in some physiological processes and the development of hepatic encephalopathy. This paper focuses on the alteration in the BBB permeability, the expression and function of ABC transporters at the BBB under liver failure status and their clinical significances. View Full-Text
Keywords: blood-brain barrier; liver failure; P-glycoprotein; breast cancer resistance protein; multidrug resistance-associated proteins; hepatic encephalopathy blood-brain barrier; liver failure; P-glycoprotein; breast cancer resistance protein; multidrug resistance-associated proteins; hepatic encephalopathy
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Fan, Y.; Liu, X. Alterations in Expression and Function of ABC Family Transporters at Blood-Brain Barrier under Liver Failure and Their Clinical Significances. Pharmaceutics 2018, 10, 102.

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