RRC ID 36768
Author Verstraelen J, Reichl S.
Title Upregulation of P-glycoprotein expression by ophthalmic drugs in different corneal in-vitro models.
Journal J. Pharm. Pharmacol.
Abstract OBJECTIVES:The purpose of this study was to analyse P-glycoprotein (P-gp) expression in different human in-vitro cornea models (HCE-T epithelial model and Hemicornea construct) after stimulation with P-gp substrates (rhodamine 123, levofloxacin and acebutolol).
METHODS:The influence of P-gp substrates on mRNA expression was analysed using reverse transcriptase polymerase chain reaction (PCR) and real-time PCR. The effect of stimulation on the transporter functionality was estimated with a digoxin efflux assay. The Caco-2 cell line was used as positive control.
KEY FINDINGS:The reverse transcriptase PCR results showed an increase in band intensity compared with the control medium for all substrates. The real-time PCR for the Caco-2 and HCE-T epithelial model yielded a similar outcome, in which all tested substrates upregulated P-gp. In contrast, the Hemicornea construct showed no significant increase in the mRNA expression after stimulation. Both in-vitro models possessed similar drug transport profiles after stimulation. A significantly increased efflux of digoxin was measured after 24 and 72 h of stimulation with levofloxacin and acebutolol.
CONCLUSIONS:The expression and functionality of the P-gp in corneal tissue can be influenced through time exposure with specific substrates. However, the exact mechanism still requires further elucidation.
Volume 67(5)
Pages 605-15
Published 2015-5
DOI 10.1111/jphp.12357
PMID 25643948
MeSH ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis* Acebutolol / pharmacology* Cells, Cultured Cornea / drug effects* Cornea / metabolism* Humans In Vitro Techniques Levofloxacin / pharmacology* Ophthalmic Solutions / pharmacology* Rhodamine 123 / pharmacology Up-Regulation / drug effects*
IF 2.39
Times Cited 3
Human and Animal Cells HCE-T(RCB2280)