ANTIOXIDANT EFFECTS OF PROPOFOL IN HUMAN HEPATIC MICROSOMES - CONCENTRATION EFFECTS AND CLINICAL RELEVANCE

Propofol is known to possess antioxidant properties. There is controve rsy regarding the mechanisms by which the drug produces its antioxidan t effects and the significance of these effects in relation to plasma concentrations of propofol in clinical practice. We studied the effect s of increasing concentrations of Intralipid, propofol, butylated hydr oxytoluene (BHT) and a vitamin E analogue (Trolox C) in 0.9% saline on non-enzymic and enzymic lipid peroxidation in human hepatic microsome s, and on concentrations of antioxidant enzymes in a Hep G2 cell line. Propofol showed significant inhibition of lipid peroxidation, but was less potent than BHT or Trolox C. IC50 values for non-enzymic and enz ymic lipid peroxidation were mean 9.47 (SD 0.86) and 7.39 (0.84) mu mo l litre(-1) for propofol, 1.30 (0.57) and 0.32 (0.02) mu mol litre(-1) for BHT and 2.34 (0.68) and 0.35 (0.04) mu mol litre(-1) for Trolox C , respectively. The antioxidant activities of propofol were substantia lly retained in the presence of up to 30 g litre(-1) of human serum al bumin. Propofol at concentrations of up to 100 mu mol litre(-1) had no significant effect on the activities of antioxidant enzymes. Clinical ly relevant concentrations of propofol produced significant inhibition of both enzymic and non-enzymic lipid peroxidation in hepatic microso mal preparations, possibly as a result of accumulation in lipophilic e nvironments. Measurement of antioxidant effects of drugs in aqueous me dia may have little relevance to their effects in protecting against l ipid peroxidation in biological systems.