Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/23480
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Type: Journal article
Title: Effect of the anti-anginal agent, perhexiline, on neutrophil, valvular and vascular superoxide formation
Author: Kennedy, J.
Beck-Oldach, K.
McFadden-Lewis, K.
Murphy, G.
Wong, Y.
Zhang, Y.
Horowitz, J.
Citation: Behavioural Processes, 2006; 531(1-3):13-19
Publisher: Elsevier Science BV
Issue Date: 2006
ISSN: 0014-2999
1879-0712
Statement of
Responsibility: 
Jennifer A. Kennedy, Konstanz Beck-Oldach, Kate McFadden-Lewis, Geraldine A. Murphy, Yee W. Wong, Yi Zhang, John D. Horowitz
Abstract: The prophylactic anti-anginal agent, perhexiline, may also be effective in acute coronary syndromes and advanced aortic valvular stenosis, conditions associated with enhanced inflammation. Its potential effects on superoxide formation via NADPH oxidase were measured by lucigenin-mediated chemiluminescence. Perhexiline inhibited superoxide formation in intact neutrophils stimulated with formyl Met Leu Phe (fMLP) 4 μM or with phorbol myristate acetate (PMA) 162 nM — IC50 2.3 μM (1.5–3.6), n = 4. Sub-unit assembly of NADPH oxidase by PMA was unaffected by pretreatment with perhexiline 2 μM, a concentration which reduced superoxide formation by 44 ± 5% (n = 4) in intact neutrophils. Perhexiline inhibited preassembled neutrophil NADPH oxidase and that in membranes of pig valve interstitial cells, human umbilical vein endothelial cells (HUVECs) and cardiac fibroblasts, but not that in rat aorta (rings or membrane preparations). These data imply that perhexiline inhibits the phagocytic NADPH oxidase directly, and that pig aortic valvular interstitial cells possess a similar enzyme, a conclusion supported by immunohistochemical localisation of the gp91phox subunit in these cells. However further study is required to clarify the effect of perhexiline on different NADPH oxidase isoforms particularly in the vasculature.
Keywords: Superoxide
NADPH oxidase
Neutrophil
Aorta
Aortic valve
HUVEC (human umbilical vein endothelial cell)
Fibroblast
Perhexiline
Description: Copyright © 2005 Elsevier B.V. All rights reserved.
DOI: 10.1016/j.ejphar.2005.11.058
Appears in Collections:Aurora harvest 6
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