Temporal and kinetic determinants of the inhibition of LDL oxidation by N-acetylcysteine (NAC)

We investigated the ability of NAC to inhibit in vitro LDL oxidation, and the effects of the timing of NAC addition, repeated additions of NAC, and the presence of preoxidized LDL, on the oxidation reaction. NAC inhibited in vitro LDL oxidation induced by copper sulfate, 2,2′-azobis(2-amidinopropane) dihydrochloride, and UV light, and protected LDL against depletion of antioxidant vitamins. Glutathione was similarly effective against copper-mediated LDL oxidation. NAC's effectiveness was inversely related to the timing of its addition. Sequential NAC additions prolonged the lag phase more effectively than initial addition of the same total dose. NAC reduced CD formation during the oxidation of native LDL by oxidized LDL. NAC's effectiveness as an inhibitor of in vitro LDL oxidation is dependent on the temporal sequence of the oxidation reaction, sequential additions, and the presence of previously oxidized LDL.