PROPOFOL ENHANCES RED-CELL ANTIOXIDANT CAPACITY IN SWINE AND HUMANS

Purpose: To determine the effect of an anaesthetic with antioxidant po tential, propofol, on red blood cell (RBC) antioxidant enzyme activiti es and RBC susceptibility to peroxidative challenge. Methods: Propofol was administered by intravenous bolus (2.5 mg.kg(-1)) and continuous infusion (36 and 72 ml.hr(-1) in nine swine; 216 ml.hr(-1) in two swin e), to achieve serum concentrations between 5 and 30 mu g.ml(-1) for t wo hours at each rate. Arterial blood sampling was at 0, 10, 30, 60, a nd 120 min for each rate of infusion, for measurement of plasma propof ol concentration, activities of plasma and RBC superoxide dismutase, g lutathione peroxidase, gluthathione reductase, RBC catalase, and RBC m alondialdehyde (MDA) formation in response to ex vivo oxidative challe nge with t-butyl hydrogen peroxide (tBHP; 1.5mM). Antioxidant mechanis ms were determined by in vitro study of MDA formation, GSH depletion, and oxidation of haemoglobin to methaemoglobin in human erythrocytes e xposed to propofol 0-75 mu M. The antioxidant potential of propofol wa s compared with that of alpha-tocopherol utilising the reaction with 2 ,4,6-tripyridyl-s-triazine (TPTZ). Results: Propofol had no effect on plasma or RBC antioxidant enzyme activities. it inhibited RBC MDA prod uction over the range of 0-20 mu g.ml(-1) (y = -18.683x + 85.431; R-2 = 0.8174). Effective propofol concentrations for 25% and 50% reduction s in MDA levels were 7-12 and 12-20 mu g.ml(-1), respectively. Propofo l has a similar effect on human erythrocytes in vitro (R-2 = 0.98). Co nclusion: Propofol antagonises the effects of forced peroxidation of r ed cells at anaesthetic and sub-anaesthetic concentrations in swine, I ts actions include scavenging of oxygen derived free radicals in a toc opherol-like manner.