Tetrahydrobiopterin inhibits copper-induced oxidation of low density lipoprotein

The effect of tetrahydrobiopterin (BPH4) on Cu2+-induced oxidation of low density lipoprotein (LDL) prepared from rabbit plasma was examined. BPH4 (0.5-10 microM) inhibited the formation of thiobarbituric acid-reactive substances (TBARS) in LDL induced by 5 microM Cu2+ in a dose-dependent manner. BPH4 also suppressed the increase in relative electrophoretic mobility (REM) of LDL in the presence of 5 microM Cu2+. The potency of inhibitions of BPH4 on TBARS formation and REM was the same as or stronger than that of ascorbic acid and alpha-tocopherol, which are known as endogenous inhibitors of LDL oxidation. These results suggest that BPH4 could act as an efficacious endogenous inhibitor of atherogenic LDL modification.