EFFECT OF URIC-ACID AND CHEMICAL ANALOGS ON OXIDATION OF HUMAN LOW-DENSITY-LIPOPROTEIN IN-VITRO

Oxidative modification of low density lipoprotein (LDL) is implicated in the early development of atherosclerosis. In the present study, att ention has been focused toward the potential protective effects of uri c acid and purine-based chemical analogues in copper-promoted oxidativ e changes to human LDL in vitro. Between 5-100 mu mol/l uric acid prot ected LDL from oxidative degradation in a concentration dependent mann er. However, 5 mu mol/l were not capable of inhibiting the consumption of LDLs natural antioxidative components, alpha-tocopherol and beta-c arotene, but led to a more than two-fold prolongation, up to 3 h, of t he lag phase before onset of polyunsaturated acid (PUFA) oxidation. 10 0 mu mol/l uric acid, which is still below the human serum level of 30 0 mu mol/l, reduced consumption of alpha-tocopherol and beta-carotene by about 50% and largely suppressed PUFA oxidation for up to 4 h. A mo re lipophilic series of methyl analogues of uric acid exhibited less a ctivity. Neither 1,3-dimethyl uric acid, nor the 1,3,7- or 1,7- or 3,7 -methylated compounds, all at 100 mu mol/l, exceeded the antioxidative potential of 10 mu mol/l uric acid. At concentrations up to 100 mu mo l/l xanthine and its analogues lacked virtually any protective effects toward the LDL constituents. In conclusion, the present study indicat es that uric acid at concentrations similar to its physiological level s, and also related analogues are able to suppress oxidative degradati on of LDL components. In view of the various mechanisms underlying ath erogenesis in vivo, the protective effect in terms of modulating redox reactions and oxidative events in the blood or at the arterial wall a ppears of potential importance. (C) 1998 Elsevier Science Inc.