ASCORBIC-ACID CAN EITHER INCREASE OR DECREASE LOW-DENSITY-LIPOPROTEIN MODIFICATION

In freshly prepared low density lipoprotein (LDL), ascorbate inhibited LDL oxidation by macrophages at the higher concentrations tested (60-100 muM). In contrast, with LDL that had been allowed to autoxidise in the refrigerator (3-degrees-C) for at least 10 weeks after isolation (mildly oxidised or minimally-modified LDL), ascorbate did not inhibit the modification of LDL in the presence of macrophages. Ascorbate actually modified autoxidised LDL itself in the absence of macrophages to greatly increase its uptake by macrophages. The modification of autoxidised LDL by ascorbate increased the levels of thiobarbituric acid-reactive substances in the medium and was completely inhibited by the antioxidant butylated hydroxytoluene. Thus the effects of ascorbate on unoxidized LDL can be very different to those on mildly oxidised LDL.