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Effects of propofol on endothelial cells subjected to a peroxynitrite donor (SIN‐1)
Author(s) -
MathyHartert M.,
MouithysMickalad A.,
Kohnen S.,
DebyDupont G.,
Lamy M.,
Hans P.
Publication year - 2000
Publication title -
anaesthesia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.839
H-Index - 117
eISSN - 1365-2044
pISSN - 0003-2409
DOI - 10.1046/j.1365-2044.2000.01606.x
Subject(s) - peroxynitrite , propofol , nitrotyrosine , tyrosine , medicine , nitric oxide , pharmacology , endothelial stem cell , biochemistry , chemistry , endocrinology , in vitro , superoxide , nitric oxide synthase , enzyme
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 m m SIN‐1, with or without 10 −3 m propofol (Diprivan®). Cytotoxicity, assessed by measuring the release of pre‐incorporated 51 Cr, 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 m m SIN‐1, respectively). Cell protection against 1 m m SIN‐1 was tested with 0.03–1.0 m m 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 m m ONOO − with 1 m m tyrosine yielded 39.6% nitrotyrosine, but nitrotyrosine was not produced when 5 m m 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.