Authors: Mathy-Hartert, M.¹; Mouithys-Mickalad, A.¹; Kohnen, S.; Deby-Dupont, G.²; Lamy, M.³; Hans, P.³

Source: Anaesthesia, Volume 55, Number 11, November 2000 , pp. 1066-1071(6)

Publisher: Wiley-Blackwell

Abstract:

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 mmSIN-1, with or without 10⁻³ mpropofol (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 mpropofol (90%, 78% and 28% of protection against 0.5, 1.0 and 2.0 mmSIN-1, respectively). Cell protection against 1 mmSIN-1 was tested with 0.03-1.0 mmpropofol 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 mmONOO⁻ with 1 mmtyrosine yielded 39.6% nitrotyrosine, but nitrotyrosine was not produced when 5 mmpropofol 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.

Keywords: Anaesthetics; intravenous; propofol

Document Type: Research article

Affiliations: 1: Research Fellow, Centre for Oxygen Research & Development, 2: Fellow, Laboratory of Homogenous Catalysis (CERM), Institutde Chimie, B6a, Research Associate and 3: Professor, Department of Anaesthesia and Intensive Care Medicine, University Hospital, B35, Domaine Universitaire du Sart Tilman, 4000 Liège, Belgium

Publication date: 2000-11-01

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