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

Abstract

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 μmol/L; 25 μg 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 μmol/L; 100 μg 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 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 α-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 Cu ²⁺ -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.