Inhibition of lipid peroxidation in isolated rat liver mitochondria by the general anaesthetic propofol.
The effect of the general anaesthetic propofol (2,6-diisopropylphenol) on lipid peroxidation in rat liver mitochondria was assessed with the thiobarbituric acid (TBA) assay. Propofol was shown to inhibit the accumulation of TBA-reactive compounds after initiation of radical production by the addition of the ADP-Fe2+ complex. Analysis of kinetics showed that propofol caused a concentration-dependent delay as well as a decrease in the rate of the peroxidation process. 1H-NMR spectra of mitochondrial lipid extracts indicated that 95% of the added propofol remained intact after 30 min incubation under conditions of low oxidative stress. The ESR spectrum of propofol incubated in the presence of EDTA-Fe2+ and H2O2 as initiators of radical production showed a radical that was most likely a decomposition product of the primary phenoxy radical of propofol. It is concluded that (a) propofol acts as a chain reaction-breaking antioxidant by forming a stable radical and (b) propofol does not seem to be metabolized in mitochondria in vitro.
Eriksson
O
O
Department of Medical Chemistry, University of Helsinki, Finland.
Pollesello
P
P
Saris
N E
NE
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects*; D008055:Lipids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D013858:Thiobarbiturates
D000975:Antioxidants; D005609:Free Radicals; D008055:Lipids; D013858:Thiobarbiturates; C029936:adenosine diphosphate-ferric chelate; D000244:Adenosine Diphosphate; C029684:thiobarbituric acid; D015742:Propofol