Ibuprofen protects low density lipoproteins against oxidative modification

Oxidative modification of LDL by vascular cells has been proposed as the me chanism by which LDL become atherogenic. The effect of ibuprofen on LDL mod ification by copper ions, monocytes and endothelial cells was studied by me asuring lipid perolridation products. Ibuprofen inhibited LDL oxidation in a dose-dependent manner over a concentration range of 0.1 to 2.0 mM. Ibupro fen (2 mM, 100 mu g/ml LDL) reduced the amount of lipid peroxides formed du ring 2 and 6 h incubation in the presence of copper ions by 52 and 28%, res pectively. Weak free radical scavenging activity of ibuprofen was observed in the DPPH test. The protective effect of ibuprofen was more marked when o xidation was induced by monocytes or endothelial cells. Ibuprofen (1 mM, 10 0 mu g/ml LDL) reduced the amount of lipid peroxides generated in LDL durin g monocyte-mediated oxidation by 40%. HUVEC-mediated oxidation of LDL in th e absence and presence of CU2+ was reduced by 32 and 39%, respectively. Mor e lipid peroxides appeared when endothelial cells were stimulated by IL-1 b eta or TNF alpha. and the inhibitory effect of ibuprofen in this case was m ore pronounced. Ibuprofen (1 mM, 100 mu g/ml LDL) reduced the amount of lip id peroxides formed during incubation of LDL with IL-1 beta-stimulated HUVE C by 43%. The figures in the absence and presence of CU2+ for HUVE stimulat ed with TNF alpha were 56 and 59%, respectively. To assess the possibility that ibuprofen acts by lowering the production rate of reactive oxygen spec ies, the intracellular concentration of H2O2 was measured. Ibuprofen (1 mM) reduced intracellular production of hydrogen peroxide in PMA-stimulated mo nonuclear cells by 69%. When HUVEC were stimulated by IL-1 beta or TNF alph a the reduction was 62% and 66%, respectively.