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Bioenergetic disruption of human micro-vascular endothelial cells by antipsychotics

Elmorsy, Ekramy; Smith, Paul A.

Authors

Ekramy Elmorsy

Paul A. Smith



Abstract

Antipsychotics (APs) are widely used medications, however these are not without side effects such as disruption of blood brain barrier function (BBB). To investigate this further we have studied the chronic effects of the typical APs, chlorpromazine (CPZ) and haloperidol (HAL) and the atypical APs, risperidone (RIS) and clozapine (CLZ), on the bioenergetics of human micro-vascular endothelial cells (HBVECs) of the BBB. Alamar blue (AB) and ATP assays showed that these APs impair bioenergenesis in HBVECs in a concentration and time dependent manner. However since these effects were incomplete they suggest a population of cell bioenergetically heterogeneous, an idea supported by the bistable nature by which APs affected the mitochondrial transmembrane potential. CPZ, HAL and CLZ inhibited the activity of mitochondrial complexes I and III. Our data demonstrates that at therapeutic concentrations, APs can impair the bioenergetic status of HBVECs, an action that help explains the adverse side effects of these drugs when used clinically.

Journal Article Type Article
Publication Date 2015-05
Journal Biochemical and Biophysical Research Communications
Print ISSN 0006-291X
Electronic ISSN 1090-2104
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 460
Issue 3
Pages 857-862
APA6 Citation Elmorsy, E., & Smith, P. A. (2015). Bioenergetic disruption of human micro-vascular endothelial cells by antipsychotics. Biochemical and Biophysical Research Communications, 460(3), 857-862. https://doi.org/10.1016/j.bbrc.2015.03.122
DOI https://doi.org/10.1016/j.bbrc.2015.03.122
Keywords Antipsychotics, Mitochondria, Blood brain barrier, Endothelia, Heterogeneity, Toxicology
Publisher URL https://doi.org/10.1016/j.bbrc.2015.03.122
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0
Additional Information This article is maintained by: Elsevier; Article Title: Bioenergetic disruption of human micro-vascular endothelial cellsbyantipsychotics; Journal Title: Biochemical and Biophysical Research Communications; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.bbrc.2015.03.122; Content Type: article; Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0





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