title: Effect of propofol and thiopentone on free radical mediated oxidative stress of the erythrocyte.
abstract: Propofol has free radical scavenging properties similar to those of recognized phenol-based antioxidants. We have examined these properties in an in vitro model of radical-induced cellular injury, comparing its activity with that of thiopentone (which has also been shown to have radical scavenging activity). Haemolysis of human erythrocytes was induced using the azo compound 2,2'-azo-bis(2-amidinopropane) dihydrochloride (ABAP). This was achieved by incubating a 10% suspension of erythrocytes with ABAP 100 mmol litre-1 at 37 degrees C. For propofol, at concentrations of 12.5, 25 and 50 mumol litre-1, the times to achieve 50% haemolysis were mean 126 (SEM 7) min (95% confidence interval 108-144 min), 150 (8) (129-170) min and 182 (12) (160-180) min, respectively (Intralipid control 107 (7) (90-125) min, ANOVA P < 0.0001). For thiopentone, at concentrations of 62.5, 125 and 250 mumol litre-1, the values were 117 (2) (112-121) min, 126 (3) (119-133) min and 138 (2) (132-144) min, respectively (saline control 109 (2) (104-113) min, ANOVA P < 0.0001). Spectroscopic analysis in the visible and ultraviolet spectra demonstrated a steady increase in the proportion of methaemoglobin during haemolysis, with the highest concentrations in the propofol-containing flasks. The formation of methaemoglobin was preceded by the generation of ferrylhaemoglobin (a Fe4+ haemoglobin species). Further experiments examining oxidation of purified methaemoglobin to ferrylhaemoglobin by hydrogen peroxide suggested that propofol, but not Intralipid or thiopentone, reduced ferrylhaemoglobin back to the met- state, and thereby explained the higher concentrations of methaemoglobin in the propofol-containing erythrocyte suspensions. We conclude that propofol is a more potent free radical scavenger in this model of oxidant stress than thiopentone, and that reduction of high oxidation states of haemoglobin may contribute to such activity.
authors.affiliation: Department of Anaesthesia, General Infirmary, Leeds.
authors.forename: P G
authors.initials: PG
authors.lastname: Murphy
authors.forename: M J
authors.initials: MJ
authors.lastname: Davies
authors.forename: M O
authors.initials: MO
authors.lastname: Columb
authors.forename: N
authors.initials: N
authors.lastname: Stratford
mesh_terms: D000328:Adult; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D018929:Cell Culture Techniques; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D016166:Free Radical Scavengers / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D015742:Propofol / Q000494:pharmacology*; D013053:Spectrophotometry; D013874:Thiopental / Q000494:pharmacology*
chemical_list: D018686:Anesthetics, Intravenous; D016166:Free Radical Scavengers; D006454:Hemoglobins; D013874:Thiopental; D015742:Propofol