Inhibitory Effects of Ketoconazole on the Oxidation of Linoleic Acid Micelles, Phospholipid Liposomes, and Human Low Density Lipoprotein (h-LDL)
Munroe, Melissa E.
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Soybean lipoxygenase (SLO) (500-5000 units/ml), Fe(III)Cl3/ascorbate (5-100microM) and hematin (5-100microM) induced oxidative modification of lipids present in micelles of linoleic acid (0.5 mM), liposomes prepared from phospholipid extracts of bovine brain (2.5 mg/ml), and h-LDL (0.5 mg/ml). Oxidation of the lipid substrates was determined by the formation of thiobarbituric acid reactive substances and conjugated dienes. Free iron (Fe(III)Cl3/ascorbate) was the strongest initiator, followed by hematin and SLO. Ketoconazole (KC) attenuated lipid oxidation in a concentration dependent manner at pharmacologically relevant levels (25-100microM) in all three substrates. Pretreatment of liposomes and h-LDL with KC produced greater attenuation of lipid oxidation by the various initiators in comparison to free KC.
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