The concentration-dependent effects of a series of lipoxygenase inhibitors and antioxidants on the macrophage-mediated oxidative modification of low-density lipoprotein (LDL) were measured. Their influence on macrophage 5-lipoxygenase pathway activity was also studied over the same concentration range. No correlation between inhibition of 5-lipoxygenase and of macrophage-mediated oxidation of LDL was observed. The capacity of the compounds to prevent cell-mediated modification of LDL could be explained in terms of their activity as either aqueous- or lipid-peroxyl radical scavengers. Two potent 5-lipoxygenase inhibitors (MK 886 and Revlon 5901), which had no radical-scavenging properties, were unable to block LDL modification. It is concluded that 5-lipoxygenase is not essential for LDL oxidation by macrophages.
