Effects of naftidrofuryl on hypoxia-induced activation and mortality of human endothelial cells.

Abstract

The present study was designed to elucidate the possible beneficial effects of naftidrofuryl on ischemia-induced endothelium damage. For this purpose, an in vitro model was developed wherein human endothelial cells isolated from umbilical vein were submitted to hypoxia. Long-term hypoxia incubation (6 h) induced cell mortality, and naftidrofuryl strongly protected endothelial cells against this mortality in a dose-dependent manner and at concentrations as low as 10(-9) M. 66% protection was still observed after 16 h of hypoxia. Naftidrofuryl had to be present during the hypoxia incubation to exert its action; preincubation up to 24 h in the presence of naftidrofuryl could not protect endothelial cells incubated under hypoxia without naftidrofuryl. Short-term hypoxia, which does not induce mortality, strongly activates the endothelial cells with an increase in the cytosolic calcium concentration, in the phospholipase A2 activity, and in the synthesis of prostaglandin and of platelet-activating factor. It also enhances the adherence of polymorphonuclear neutrophils. Naftidrofuryl was able to markedly inhibit this whole cascade of events in a dose-dependent manner. We also demonstrated that naftidrofuryl could block the decrease in ATP concentration that results from the hypoxic conditions. These results indicate that by preserving the energetic level of the cells, naftidrofuryl prevents the activation of endothelial cells and the cell mortality induced by hypoxia. By maintaining an intact endothelium in vivo during ischemia, naftidrofuryl could prevent the further damage induced by leukocyte recruitment and activation.

• Authors: C Michiels, T Arnould, D Janssens, I Alexandre, A Houbion, J Remacle
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 267 Issue 2 Pg. 904-11 (Nov 1993) ISSN: 0022-3565 [Print] United States
• PMID: 8246166 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Prostaglandins
• Arachidonic Acid
• Nafronyl
• Adenosine Triphosphate
• Phospholipases A
• Phospholipases A2
• Calcium

Topics

• Adenosine Triphosphate (metabolism)
• Arachidonic Acid (metabolism)
• Calcium (metabolism)
• Cell Death (drug effects)
• Cell Hypoxia (physiology)
• Cells, Cultured
• Cytosol (metabolism)
• Endothelium, Vascular (cytology, drug effects, physiology)
• Enzyme Activation
• Humans
• Ischemia (drug therapy, enzymology, metabolism)
• Models, Biological
• Nafronyl (pharmacology)
• Phospholipases A (drug effects, metabolism)
• Phospholipases A2
• Prostaglandins (metabolism)