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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:2855-2860.)
© 1997 American Heart Association, Inc.

Articles

Paracetamol Catalyzes Myeloperoxidase-Initiated Lipid Oxidation in LDL

S. Kapiotis; G. Sengoelge; M. Hermann; I. Held; C. Seelos; ; B. M. K. Gmeiner

From the Clinical Institute of Medical and Chemical Laboratory Diagnostics (S.K.), the Department of Internal Medicine III, Division of Nephrology and Dialysis (G.S.), the Institute of Molecular Genetics (M.H.), the Institute of Tumor Biology and Cancer Research (C.S.), and the Institute of Medical Chemistry (I.H., B.M.K.G.), University of Vienna, Vienna, Austria

Correspondence to Bernhard Gmeiner, Institute of Medical Chemistry, University of Vienna, Währingerstr. 10, A-1090 Vienna, Austria.

Abstract The oxidative modification of LDL may play a significant role in atherogenesis. Myeloperoxidase (MPO) expressed in human atherosclerotic plaques has been suggested to be operative in vivo, making LDL atherogenic. Tyrosyl radicals generated by MPO have been shown to act as physiological pro-oxidants of lipid peroxidation in LDL. Assuming that a variety of phenolic compounds are able to form phenoxyl radicals when exposed to peroxidases, we tested the ability of paracetamol, a known analgesic drug with a tyrosine-like monophenolic structure, to act as a pro-oxidant of lipid peroxidation in LDL. Spectroscopic analyses indicated that paracetamol, similar to tyrosine, could undergo peroxidase-induced phenoxyl radical formation, which was inhibited by the radical scavenger ascorbic acid as well as by heme poisons and catalase. Measurement of conjugated dienes and lipid hydroperoxides in LDL preparations exposed to MPO/H₂O₂ in the absence or presence of paracetamol revealed that the drug could act as a catalyst of lipid oxidation in LDL. Similar results were found when LDL oxidation was performed with activated human neutrophils, which use MPO to promote lipid peroxidation. In conclusion, the results suggest that paracetamol could act, via a phenoxyl radical, as a catalyst of LDL oxidative modification by MPO.

Key Words: lipid peroxidation • myeloperoxidase • oxidized LDL • atherosclerosis • acetaminophen • paracetamol

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