Sa. Hulea et al., BILIRUBIN SENSITIZED PHOTOOXIDATION OF HUMAN PLASMA LOW-DENSITY-LIPOPROTEIN, Biochimica et biophysica acta, L. Lipids and lipid metabolism, 1304(3), 1996, pp. 197-209
Previous investigations have shown that the bile pigment bilirubin can
act as peroxyl radicals scavenger and transition metals trap, but als
o as a prooxidant, to erythrocyte ghost membranes through O-1(2)-drive
n photooxidation. In the present study we examined the changes occurri
ng in the lipoprotein particle following bilirubin-sensitized photooxi
dation of isolated plasma LDL. The oxidative stress resulted in increa
sed TBA reactivity, diene formation, free cholesterol oxidation, apo B
fragmentation and enhanced uptake of the modified particle by the mou
se macrophage scavenger receptors as well as the decrease binding to t
he native B, E-receptor on fibroblasts. The marked increase in TBARS p
roduction in D2O-enriched medium and the inhibition of lipid peroxidat
ion of azide is consistent with singlet oxygen involvement in the oxid
ation process. The apo B-bound Cu2+ appears to become redox active dur
ing photooxidation since the presence of EDTA in the reaction mixture
greatly reduced protein fragmentation. It was also found that BHT inhi
bited almost completely the lipid peroxidation, as determined by the T
BA reaction but could not totally abolish the formation of 5 alpha-hyd
roxycholesterol, which is the main product formed by the direct attack
of O-1(2) on cholesterol. The results of this work strongly suggest t
hat, through photooxidation by light-activated bilirubin, the lipoprot
ein particle may be modified in the blood stream as well, besides bein
g modified in the well known oxidation site within the arterial wall.
Our findings provide the rationale for extending these studies to clin
ical investigations, which aim at developing strategies for minimizing
damage to arterial tissue following phototherapy of hyperbilirubinemi
c newborns or cancer patients after systemic administration of photose
nsitizers.