Sa. Hulea et al., INHIBITION OF METAL-CATALYZED OXIDATION OF LOW-DENSITY-LIPOPROTEIN BYFREE AND ALBUMIN-BOUND BILIRUBIN, Biochimica et biophysica acta, L. Lipids and lipid metabolism, 1259(1), 1995, pp. 29-38
Both free and albumin-bound bilirubin are known to scavenge peroxyl ra
dicals in vitro. In the present work we showed that free and albumin-b
ound bilirubin at the physiological concentration of the bile pigment
in blood plasma could greatly inhibit the metal-catalyzed oxidation of
low density lipoprotein (LDL) as shown by the reduced thiobarbituric
acid reactivity, smaller or no shifts in electrophoretic mobility, les
s apo B fragmentation and a decreased amount of cholesterol oxidation
products as detected by gas chromatography. Free bilirubin (BR) was mo
re effective in inhibiting the production of thiobarbituric acid react
ive substances in iron-catalyzed LDL peroxidation as compared to the c
opper-catalyzed reaction up to a BR to metal molar ratio of 4:1. Above
this ratio the same degree of inhibition was observed for both metal
ions. It was found that serum albumin provided full protection against
Cu2+-dependent oxidative stress only at very high protein to metal mo
lar ratio, i.e., 30:1, that is similar to that in human plasma. Comple
xation of BR to albumin brought about a marked increase in the capacit
y of the complex to bind metal ions, particularly iron, as opposed to
albumin alone. At a molar ratio of metal ion to albumin-BR of 1:1 the
inhibition of lipid peroxidation was about 96% and it was almost compl
ete at a molar ratio of 1:2. The ability of albumin-BR complex to inhi
bit effectively the transition metals-dependent oxidative stress could
be important in the extravascular space where local concentrations of
metal ions may exceed the protein binding capacity. In addition, the
strong binding of iron to the albumin-BR complex may be clinically imp
ortant, especially in iron loaded sera of hemochromatosis patients, wh
ere the transferrin is fully saturated with this ion and the free iron
could catalyze lipid peroxidation unless bound by a metal trapping de
vice such as the albumin-BR complex.