title: Paracetamol inhibits copper ion-induced, azo compound-initiated, and mononuclear cell-mediated oxidative modification of LDL.
abstract: The effects of paracetamol and sodium salicylate on the susceptibility of LDL to oxidative modification were studied. LDL was subjected to Cu(2+)-, azo compound-, or peripheral blood mononuclear cell-initiated oxidation in the absence and presence of paracetamol and salicylate. Paracetamol (100 mumol/L; 25 micrograms LDL/mL) reduced the rate of formation of conjugated dienes and the amount of conjugated dienes formed during Cu(2+)-induced oxidation by 67% and 58%, respectively. Paracetamol (400 mumol/L; 100 micrograms LDL/mL) reduced the generation of lipid peroxides during Cu(2+)-induced oxidation by 43% (P < .05), the relative electrophoretic mobility in agarose gels by 16% (P < .05), and the amount of oxidized LDL taken up by J774 macrophages by 22% (P < .05). Paracetamol (100 mumol/L; 100 micrograms LDL/mL) reduced the 2,2'-azobis-(2-amidinopropane hydrochloride)-initiated lipid peroxidation by 70% (P < .05) and the relative electrophoretic mobility by 34% (P < .05). Paracetamol (100 mumol/L; 100 micrograms LDL/mL) reduced the amount of lipid peroxides generated in LDL during mononuclear cell-mediated oxidation by 69% (P < .01) and the relative electrophoretic mobility by 38% (P < .01). In comparison, 10 mumol/L alpha-tocopherol reduced the amount of lipid peroxides formed during cellular LDL oxidation and the relative electrophoretic mobility by 52% and 65%, respectively (P < .05). In the absence of paracetamol, SOD and catalase inhibited the modification of LDL (P < .05), suggesting that superoxide anions and hydrogen peroxide might be involved in the cell-mediated modification pathway. In the presence of paracetamol, SOD showed no additional inhibitory effect.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Institute for Nutrition Research, University of Oslo, Norway.
authors.forename: M S
authors.initials: MS
authors.lastname: Nenseter
authors.forename: B
authors.initials: B
authors.lastname: Halvorsen
authors.forename: O
authors.initials: O
authors.lastname: Rosvold
authors.forename: A C
authors.initials: AC
authors.lastname: Rustan
authors.forename: C A
authors.initials: CA
authors.lastname: Drevon
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D000578:Amidines / Q000494:pharmacology*; D015764:Bepridil / Q000031:analogs & derivatives; D001713:Biphenyl Compounds; D002374:Catalase / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology*; D016166:Free Radical Scavengers; D006801:Humans; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D010851:Picrates; D012459:Salicylates / Q000494:pharmacology; D020156:Salicylic Acid; D013482:Superoxide Dismutase / Q000494:pharmacology
chemical_list: D000578:Amidines; D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D008077:Lipoproteins, LDL; D010851:Picrates; D012459:Salicylates; D000082:Acetaminophen; C046728:2,2'-azobis(2-amidinopropane); D015764:Bepridil; D003300:Copper; C004931:1,1-diphenyl-2-picrylhydrazyl; D002374:Catalase; D013482:Superoxide Dismutase; D020156:Salicylic Acid