Activity of the lipoxygenase inhibitor 1-phenyl-3-pyrazolidinone (phenidone) and derivatives on the inhibition of adhesion molecule expression on human umbilical vascular endothelial cells
Torsten Hans Schroeder, Wolfgang Artur Krueger, Hans-Jürgen Dieterich, Boris NohéDepartment of Anaesthesiology and Critical Care Medicine, Tuebingen University Hospital, Tuebingen, GermanyAbstract: Leukocyte adhesion contributes to perfusion abnormalities and tissue damag...
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Dove Medical Press
2008
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oai:doaj.org-article:72685f73813043e094e6ad592543aded2021-12-02T06:29:57ZActivity of the lipoxygenase inhibitor 1-phenyl-3-pyrazolidinone (phenidone) and derivatives on the inhibition of adhesion molecule expression on human umbilical vascular endothelial cells1177-54751177-5491https://doaj.org/article/72685f73813043e094e6ad592543aded2008-03-01T00:00:00Zhttp://www.dovepress.com/activity-of-the-lipoxygenase-inhibitor-1-phenyl-3-pyrazolidinone-pheni-a64https://doaj.org/toc/1177-5475https://doaj.org/toc/1177-5491Torsten Hans Schroeder, Wolfgang Artur Krueger, Hans-Jürgen Dieterich, Boris NohéDepartment of Anaesthesiology and Critical Care Medicine, Tuebingen University Hospital, Tuebingen, GermanyAbstract: Leukocyte adhesion contributes to perfusion abnormalities and tissue damage during trauma, shock or overwhelming inflammation. This study was performed to determine whether the lipoxygenase inhibitor phenidone and derivatives decrease the expression of adhesion molecules on tumor necrosis factor-α (TNF-α) stimulated endothelial cells and attenuate leukocyte-endothelial interactions under flow in vitro. TNF-α stimulated human umbilical venous endothelial cells (HUVECs) were incubated with phenidone, 4-methyl-phenidone, 4-4-dimethyl-phenidone, 5-methyl-phenidone, 5-phenyl-phenidone, and 5-methyl-1,(2,5-dichloro-phenyl)-3-pyrazolidone. We tested the inhibition of adhesion molecule expression at different inhibitor concentrations before, during, and after the stimulation of HUVECs. The inhibition of endothelial cell expression on HUVECs was measured by flow cytometry. Rolling and firm adhesion of leukocytes to pretreated endothelium was examined in a parallel plate flow chamber. Phenidone inhibited the expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial-leukocyte adhesion molecule-1 on HUVECs when added prior to HUVEC stimulation. The inhibitory effect of phenidone was still observed when added simultaneously, but not when added after HUVEC stimulation. 4-4-dimethyl-phenidone and 5-phenyl-phenidone inhibited the expression of adhesion molecules more effectively than phenidone. The attenuation of leukocyte rolling under flow conditions was also significantly more effective with 4-4-dimethyl-phenidone than with phenidone. Lipoxygenase inhibitors might be of therapeutically interest for the treatment of overwhelming systemic inflammation during shock, trauma, and sepsis.Keywords: lipoxygenase inhibitor, adhesion molecules, vascular endothelial cells, TNF-α, SIRS Torsten Hans SchroederWolfgang Artur KruegerHans-Jürgen DieterichBoris NohéDove Medical PressarticleMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol 2008, Iss Issue 1, Pp 151-160 (2008) |
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Medicine (General) R5-920 |
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Medicine (General) R5-920 Torsten Hans Schroeder Wolfgang Artur Krueger Hans-Jürgen Dieterich Boris Nohé Activity of the lipoxygenase inhibitor 1-phenyl-3-pyrazolidinone (phenidone) and derivatives on the inhibition of adhesion molecule expression on human umbilical vascular endothelial cells |
| description |
Torsten Hans Schroeder, Wolfgang Artur Krueger, Hans-Jürgen Dieterich, Boris NohéDepartment of Anaesthesiology and Critical Care Medicine, Tuebingen University Hospital, Tuebingen, GermanyAbstract: Leukocyte adhesion contributes to perfusion abnormalities and tissue damage during trauma, shock or overwhelming inflammation. This study was performed to determine whether the lipoxygenase inhibitor phenidone and derivatives decrease the expression of adhesion molecules on tumor necrosis factor-α (TNF-α) stimulated endothelial cells and attenuate leukocyte-endothelial interactions under flow in vitro. TNF-α stimulated human umbilical venous endothelial cells (HUVECs) were incubated with phenidone, 4-methyl-phenidone, 4-4-dimethyl-phenidone, 5-methyl-phenidone, 5-phenyl-phenidone, and 5-methyl-1,(2,5-dichloro-phenyl)-3-pyrazolidone. We tested the inhibition of adhesion molecule expression at different inhibitor concentrations before, during, and after the stimulation of HUVECs. The inhibition of endothelial cell expression on HUVECs was measured by flow cytometry. Rolling and firm adhesion of leukocytes to pretreated endothelium was examined in a parallel plate flow chamber. Phenidone inhibited the expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial-leukocyte adhesion molecule-1 on HUVECs when added prior to HUVEC stimulation. The inhibitory effect of phenidone was still observed when added simultaneously, but not when added after HUVEC stimulation. 4-4-dimethyl-phenidone and 5-phenyl-phenidone inhibited the expression of adhesion molecules more effectively than phenidone. The attenuation of leukocyte rolling under flow conditions was also significantly more effective with 4-4-dimethyl-phenidone than with phenidone. Lipoxygenase inhibitors might be of therapeutically interest for the treatment of overwhelming systemic inflammation during shock, trauma, and sepsis.Keywords: lipoxygenase inhibitor, adhesion molecules, vascular endothelial cells, TNF-α, SIRS |
| format |
article |
| author |
Torsten Hans Schroeder Wolfgang Artur Krueger Hans-Jürgen Dieterich Boris Nohé |
| author_facet |
Torsten Hans Schroeder Wolfgang Artur Krueger Hans-Jürgen Dieterich Boris Nohé |
| author_sort |
Torsten Hans Schroeder |
| title |
Activity of the lipoxygenase inhibitor 1-phenyl-3-pyrazolidinone (phenidone) and derivatives on the inhibition of adhesion molecule expression on human umbilical vascular endothelial cells |
| title_short |
Activity of the lipoxygenase inhibitor 1-phenyl-3-pyrazolidinone (phenidone) and derivatives on the inhibition of adhesion molecule expression on human umbilical vascular endothelial cells |
| title_full |
Activity of the lipoxygenase inhibitor 1-phenyl-3-pyrazolidinone (phenidone) and derivatives on the inhibition of adhesion molecule expression on human umbilical vascular endothelial cells |
| title_fullStr |
Activity of the lipoxygenase inhibitor 1-phenyl-3-pyrazolidinone (phenidone) and derivatives on the inhibition of adhesion molecule expression on human umbilical vascular endothelial cells |
| title_full_unstemmed |
Activity of the lipoxygenase inhibitor 1-phenyl-3-pyrazolidinone (phenidone) and derivatives on the inhibition of adhesion molecule expression on human umbilical vascular endothelial cells |
| title_sort |
activity of the lipoxygenase inhibitor 1-phenyl-3-pyrazolidinone (phenidone) and derivatives on the inhibition of adhesion molecule expression on human umbilical vascular endothelial cells |
| publisher |
Dove Medical Press |
| publishDate |
2008 |
| url |
https://doaj.org/article/72685f73813043e094e6ad592543aded |
| work_keys_str_mv |
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