Evaluation of the antioxidative properties of lipoxygenase inhibitors

Background: oxidative stress is a component of many pathological conditions including neurodegenerative diseases and inflammation. an important source of reactive oxygen species (ros) are lipoxygenases (lox) - enzymes responsible for the metabolism of arachidonic acid and other polyunsaturated fatty acids. lox inhibitors have a protective effect in inflammatory diseases and in neurodegenerative disorders because of their anti-inflammatory activity. however,the molecular mechanism of the protective action of lox inhibitors has not yet been fully elucidated. methods: the aim of this study was to compare the antioxidative potential of widely used lox inhibitors: bwb70c,aa-861,zileuton,baicalein and ndga. the antioxidative properties were evaluated in cell-free systems. we measured the effect of the tested compounds on iron/ascorbate-induced lipid peroxidation and on carbonyl group formation in the rat brain homogenate. direct free radical scavenging was analyzed by using dpph assay. results: our data showed that the inhibitor of all loxs,i.e.,ndga,5-lox inhibitor bwb70c and the inhibitor of 12/15-lox,baicalein,significantly decreased the level of lipid and protein oxidation. the free radical scavenging activity of these inhibitors was comparable to known ros scavengers,i.e.,resveratrol and trolox. zileuton (the inhibitor of 5-lox) slightly prevented lipid and protein oxidation,it also scavenged the dpph radical. aa-861 (the inhibitor of 5 and 12/15-lox) slightly protected lipids against fe/asc-evoked lipid peroxidation at high concentrations,but had no effect on carbonyl group formation and dpph scavenging. conclusions: our results indicate that some lox inhibitors demonstrate potent anti-oxidative,free radical scavenging properties. aa-861,whose antioxidative potential is very weak,may be a specific tool to be used in experimental and perhaps even clinical applications. copyright © 2012 by institute of pharmacology polish academy of sciences.