Effects of propofol on endothelial cells subjected to a peroxynitrite donor (SIN-1).
We investigated the effect of propofol on endothelial cells subjected to the peroxynitrite (ONOO-) donor 3-morpholino sydnonimine (SIN-1). Cells were incubated overnight with 0.5, 1.0 or 2.0 mM SIN-1, with or without 10-3 M propofol (Diprivan). Cytotoxicity, assessed by measuring the release of pre-incorporated 51Cr, increased when the concentration of SIN-1 increased, and was significantly decreased by 10-3 M propofol (90%, 78% and 28% of protection against 0.5, 1.0 and 2.0 mM SIN-1, respectively). Cell protection against 1 mM SIN-1 was tested with 0.03-1.0 mM propofol and this was compared to tyrosine, a target molecule for peroxynitrite. Propofol protected cells in a dose-dependent manner (r = 0.98; p < 0.001) and was as effective as tyrosine. Finally, using high-performance liquid chromatography, we demonstrated that propofol reacted with ONOO- more rapidly than did tyrosine, inhibiting nitrotyrosine formation. In the absence of propofol, 3.5 mM ONOO- with 1 mM tyrosine yielded 39.6% nitrotyrosine, but nitrotyrosine was not produced when 5 mM propofol was added. We conclude that propofol protects endothelial cells against the toxicity of ONOO-. The anti-oxidant properties of propofol can be partially attributed to its scavenging effect on peroxynitrite, a property that might be relevant in pathological situations involving a significant contribution of peroxynitrite to tissue damage.
Mathy-Hartert
M
M
Centre for Oxygen Research & Development, Institutde Chimie, Domaine Universitaire du Sart Tilman, Liège, Belgium.
Mouithys-Mickalad
A
A
Kohnen
S
S
Deby-Dupont
G
G
Lamy
M
M
Hans
P
P
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D018929:Cell Culture Techniques; D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009566:Nitrates / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology*; D014443:Tyrosine / Q000378:metabolism / Q000494:pharmacology
D018686:Anesthetics, Intravenous; D009566:Nitrates; D020030:Nitric Oxide Donors; C039642:peroxynitric acid; D014443:Tyrosine; C002385:linsidomine; D008981:Molsidomine; D015742:Propofol