British Journal of Anaesthesia, Vol 81, Issue 4 584-589, Copyright © 1998 by The Board of Management and Trustees of the British Journal of Anaesthesia
Y. P. Bao, G. Williamson, D. Tew, G. W. Plumb, N. Lambert, J. G. Jones and D. K. Menon
Propofol is known to possess antioxidant properties. There is controversy
regarding the mechanisms by which the drug produces its antioxidant effects
and the significance of these effects in relation to plasma concentrations
of propofol in clinical practice. We studied the effects of increasing
concentrations of Intralipid, propofol, butylated hydroxytoluene (BHT) and
a vitamin E analogue (Trolox C) in 0.9% saline on non-enzymic and enzymic
lipid peroxidation in human hepatic microsomes, 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 enzymic lipid peroxidation were mean 9.47
(SD 0.86) and 7.39 (0.84) microgramsmol litre-1 for propofol, 1.30 (0.57)
and 0.32 (0.02) microgramsmol litre-1 for BHT and 2.34 (0.68) and 0.35
(0.04) microgramsmol litre-1 for Trolox C, respectively. The antioxidant
activities of propofol were substantially retained in the presence of up to
30 g litre-1 of human serum albumin. Propofol at concentrations of up to
100 microgramsmol litre-1 had no significant effect on the activities of
antioxidant enzymes. Clinically relevant concentrations of propofol
produced significant inhibition of both enzymic and non-enzymic lipid
peroxidation in hepatic microsomal preparations, possibly as a result of
accumulation in lipophilic environments. Measurement of antioxidant effects
of drugs in aqueous media may have little relevance to their effects in
protecting against lipid peroxidation in biological systems.
LABORATORY INVESTIGATIONS
Antioxidant effects of propofol in human hepatic microsomes: concentration effects and clinical relevance
Biochemistry Department, Institute of Food Research, Colney, Norwich NR4 7UA; Department of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ
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