Paracetamol catalyzes myeloperoxidase-initiated lipid oxidation in LDL.
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.
Kapiotis
S
S
Clinical Institute of Medical and Chemical Laboratory Diagnostics, University of Vienna, Austria.
Sengoelge
G
G
Hermann
M
M
Held
I
I
Seelos
C
C
Gmeiner
B M
BM
D000082:Acetaminophen / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001386:Azides / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D002384:Catalysis; D003486:Cyanides / Q000494:pharmacology; D019281:Dimerization; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology; D016877:Oxidants / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000737:chemistry
D000975:Antioxidants; D001386:Azides; D003486:Cyanides; D016166:Free Radical Scavengers; D008077:Lipoproteins, LDL; D016877:Oxidants; C099252:oxidized low density lipoprotein; D000082:Acetaminophen; D014443:Tyrosine; D006861:Hydrogen Peroxide; D002374:Catalase; D009195:Peroxidase; D001205:Ascorbic Acid