Bioenergetic disruption of human micro-vascular endothelial cells by antipsychotics

Elmorsy, Ekramy; Smith, Paul A.

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.

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

• Journal Article Type: Article
• Acceptance Date: Mar 12, 2015
• Online Publication Date: Mar 28, 2015
• Publication Date: 2015-05
• Deposit Date: Jun 1, 2017
• Publicly Available Date: Jun 1, 2017
• 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
• DOI: https://doi.org/10.1016/j.bbrc.2015.03.122
• Keywords: Antipsychotics, Mitochondria, Blood brain barrier, Endothelia, Heterogeneity, Toxicology
• Public URL: https://nottingham-repository.worktribe.com/output/752417
• Publisher URL: https://doi.org/10.1016/j.bbrc.2015.03.122
• 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.
• Contract Date: Jun 1, 2017