PARACETAMOL INHIBITS COPPER ION-INDUCED, AZO COMPOUND-INITIATED, AND MONONUCLEAR CELL-MEDIATED OXIDATIVE MODIFICATION OF LDL

The effects of paracetamol and sodium salicylate on the susceptibility of LDL to oxidative modification were studied. LDL was subjected to C u2+-, azo compound-, or peripheral blood mononuclear cell-initiated ox idation in the absence and presence of paracetamol and salicylate. Par acetamol (100 mu mol/L; 25 mu g 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 mu mol/L; 100 mu g LDL/mL) reduced the generation of lipid peroxides during Cu2+-induced oxidation by 43% (P < .05), the relative electroph oretic mobility in agarose gels by 16% (P < .05), and the amount of ox idized LDL taken up by J774 macrophages by 22% (P < .05). Paracetamol (100 mu mol/L; 100 pg 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 m u mol/L; 100 mu g LDL/mL) reduced the amount of lipid peroxides genera ted in LDL during mononuclear cell-mediated oxidation by 69% (P < .01) and the relative electrophoretic mobility by 38% (P < .01). In compar ison, 10 mu mol/L alpha-tocopherol reduced the amount of lipid peroxid es formed during cellular LDL oxidation and the relative electrophoret ic 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-diph enyl-2-pikrylhydracyl radical-scavenging test showed that paracetamol itself was a free-radical scavenger. In contrast, sodium salicylate (2 5 to 4000 mu mol/L) showed no free radical-scavenging property and fai led to protect LDL against mononuclear cell-mediated oxidation. In con clusion, the results indicate that paracetamol, but not salicylate, pr otects LDL against Cu2+-induced, azo compound-initiated, and mononucle ar cell-mediated oxidative modification in vitro and that this may be due to the radical scavenger capacity of paracetamol.