Comparison of HOCl traps with myeloperoxidase inhibitors in prevention of low density lipoprotein oxidation

In this study, the production of the highly toxic oxidant hypochlorous acid (HOCl) by the phagocytic enzyme myeloperoxidase (MPO) was quantitated and the concomitant alterations of low density lipoprotein (LDL) were analyzed in view of the potential role of LDL in atherosclerosis. Using the monochlo rodimedone assay, it was found that HOCl is produced in micromolar concentr ations, The kinetics of the decrease of tryptophan fluorescence appeared to be a sensitive method to monitor LDL alterations under near in vivo condit ions. Therefore, this method was used to subsequently compare the effective ness of MPO inhibitors that block production of HOCl with compounds that ac t as HOCl traps. The efficiency of MPO inhibitors to prevent LDL damage inc reased in the series benzohydroxamic acid < salicylhydroxamic acid < 3-amin o-1,2,4-triazole < sodium azide < potassium cyanide < p-hydroxy-benzoic aci d hydrazide, while for the HOCl traps the protective efficiency increased i n the series glycine < taurine < methionine. We conclude that HOCl traps ma y have high potential therapeutic impact in vivo due to their low toxicity, although high concentrations of them would have to reach sites of inflamma tion. In contrast, only low concentrations of a specific MPO inhibitor woul d be required to irreversibly inhibit the enzyme. (C) 2000 Elsevier Science B.V. All rights reserved.