This Article Full Text Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nenseter, M. S. Articles by Drevon, C. A. Search for Related Content PubMed PubMed Citation Articles by Nenseter, M. S. Articles by Drevon, C. A.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:1338-1344.)
© 1995 American Heart Association, Inc.

Articles

Paracetamol Inhibits Copper Ion–Induced, Azo Compound–Initiated, and Mononuclear Cell–Mediated Oxidative Modification of LDL

Marit S. Nenseter; Bente Halvorsen; Øyvind Rosvold; Arild C. Rustan; Christian A. Drevon

From the Institute for Nutrition Research (M.S.N., B.H., C.A.D.) and the Department of Pharmacology, Institute of Pharmacy (Ø.R., A.C.R.), University of Oslo, Oslo, Norway.

Correspondence to Marit S. Nenseter, Institute for Nutrition Research, University of Oslo, PO Box 1046, Blindern, 0316 Oslo, Norway. E-mail marit.nenseter@basalmed.uio.no.

Abstract The effects of paracetamol and sodium salicylate on the susceptibility of LDL to oxidative modification were studied. LDL was subjected to Cu²⁺-, azo compound–, or peripheral blood mononuclear cell–initiated oxidation in the absence and presence of paracetamol and salicylate. Paracetamol (100 µmol/L; 25 µg LDL/mL) reduced the rate of formation of conjugated dienes and the amount of conjugated dienes formed during Cu²⁺-induced oxidation by 67% and 58%, respectively. Paracetamol (400 µmol/L; 100 µg LDL/mL) reduced the generation of lipid peroxides during Cu²⁺-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 µmol/L; 100 µg 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 µmol/L; 100 µg 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 µmol/L -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. The 1,1-diphenyl-2-pikrylhydracyl radical–scavenging test showed that paracetamol itself was a free-radical scavenger. In contrast, sodium salicylate (25 to 4000 µmol/L) showed no free radical–scavenging property and failed to protect LDL against mononuclear cell–mediated oxidation. In conclusion, the results indicate that paracetamol, but not salicylate, protects LDL against Cu²⁺-induced, azo compound–initiated, and mononuclear cell–mediated oxidative modification in vitro and that this may be due to the radical scavenger capacity of paracetamol.

Key Words: oxidized LDL • lipid peroxidation • atherosclerosis • acetylsalicylic acid • acetaminophen

This article has been cited by other articles:

				R. Golfetti, T. Rork, and G. Merrill Chronically Administered Acetaminophen and the Ischemia/Reperfused Myocardium Experimental Biology and Medicine, June 1, 2003; 228(6): 674 - 682. [Abstract] [Full Text] [PDF]

				I. R. Brude, C. A. Drevon, I. Hjermann, I. Seljeflot, S. Lund-Katz, K. Saarem, B. Sandstad, K. Solvoll, B. Halvorsen, H. Arnesen, et al. Peroxidation of LDL From Combined-Hyperlipidemic Male Smokers Supplied With Ż-3 Fatty Acids and Antioxidants Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 2576 - 2588. [Abstract] [Full Text]

				S. Kapiotis, G. Sengoelge, M. Hermann, I. Held, C. Seelos, and B. M. K. Gmeiner Paracetamol Catalyzes Myeloperoxidase-Initiated Lipid Oxidation in LDL Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 2855 - 2860. [Abstract] [Full Text]