Effects of propofol on endothelial cells subjected to a peroxynitrite donor (SIN-1)

We investigated the effect of propofol on endothelial cells subjected to th e 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 (R)). Cytotoxicity, assessed by measuring the release o f pre-incorporated Cr-51, increased when the concentration of SIN-1 increas ed, 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 protec tion against 1 mm SIN-1 was tested with 0.03-1.0 mm propofol and this was c ompared to tyrosine, a target molecule for peroxynitrite. Propofol protecte d cells in a dose-dependent manner (r = 0.98; p < 0.001) and was as effecti ve as tyrosine. Finally, using high-performance liquid chromatography, we d emonstrated that propofol reacted with ONOO- more rapidly than did tyrosine , inhibiting nitrotyrosine formation. In the absence of propofol, 3.5 mm ON OO- with 1 mm tyrosine yielded 39.6% nitrotyrosine, but nitrotyrosine was n ot produced when 5 mm propofol was added. We conclude that propofol protect s endothelial cells against the toxicity of ONOO-. The anti-oxidant propert ies of propofol can be partially attributed to its scavenging effect on per oxynitrite, a property that might be relevant in pathological situations in volving a significant contribution of peroxynitrite to tissue damage.