The Effects of Clioquinol on P-glycoprotein Expression and Biometal Distribution in the Mouse Brain Microvasculature
Mitchell P McInerney, Yijun Pan, Irene Volitakis, Ashley I Bush, Jennifer L Short, Joseph A Nicolazzo
Journal of Pharmaceutical Sciences | ELSEVIER SCIENCE INC | Published : 2019
Previous studies have demonstrated that the ionophore clioquinol (CQ), in conjunction with the biometals copper and zinc, increases the expression of P-glycoprotein (P-gp) in human cerebral microvascular endothelial (hCMEC/D3) cells. As P-gp expression and function at the blood-brain barrier (BBB) is of great interest regarding CNS drug access and endogenous toxin trafficking (e.g., amyloid beta), the present study assessed the in vivo translation of these previous in vitro findings. Swiss outbred mice received an 11-day treatment of CQ (30 mg/kg) by oral gavage, after which brain microvessel-enriched fractions (MEFs) and surrounding interfaces (subcortical brain tissue and plasma) were extr..View full abstract
Awarded by NHMRC Project
The studies completed within this publication were funded by the following sources: NHMRC Project APP1048855; the Mason Foundation; and the Bethlehem Griffiths Research Foundation. M.P.M. was supported by an Australian Government Research Training Program Scholarship. A.I.B. is a NHMRC Senior Professorial Research Fellow.