Potential role of conjugated bilirubin and copper in the metabolism of lipid peroxides in bile.

Abstract

Conjugated bilirubin and copper ions at their physiological concentrations in bile may play an important role in hydroperoxide and other detoxification. Conjugated bilirubin may also be an important chain-breaking antioxidant preventing lipid peroxidation. Bilirubin ditaurine (BR-DT), a water-soluble model compound of conjugated bilirubin, completely prevents the peroxyl radical-induced oxidation of phosphatidylcholine in either multilamellar liposomes or micelles. This antioxidant activity is associated with the bilirubin moiety of BR-DT, since taurine alone is inefficient in scavenging peroxyl radicals. The number of peroxyl radicals trapped per molecule of BR-DT is 1.9, compared to 4.7 trapped per molecule of biliverdin, the water-soluble physiological precursor of bilirubin. Peroxyl radical-induced oxidation of BR-DT results in a spectral shift in maximal absorbance toward shorter wavelengths; biliverdin is not formed as a major oxidation product. BR-DT, but neither taurine nor biliverdin, greatly accelerates the cupric ion-catalyzed decomposition of linoleic acid hydroperoxide. In the presence of ferric ion, BR-DT shows no lipid hydroperoxide-degrading activity. Addition of cupric ion to BR-DT results in formation of a complex with spectral features similar to that of a biliverdin-cupric ion complex, indicating that BR-DT and cupric ion undergo redox reactions.

Unconjugated Bilirubin Inhibits VCAM-1-Mediated Transendothelial Leukocyte Migration

“…Whether these differences in permeation are related to the inability of BDT to modulate lymphocyte migration is unknown at this time, but remains an intriguing possibility. Alternatively, these findings may be explained by the fact that the potency of BDT as an antioxidant is inferior to that of bilirubin or biliverdin (59).…”

Biliverdin inhibits activation of NF‐κB: Reversal of inhibition by human biliverdin reductase

“…The HO isozymes, HO-1 and HO-2, specifically cleave the heme molecule at the a-meso carbon bridge to yield CO and biliverdin IXa; the open tetrapyrrole is subsequently reduced by BVR to bilirubin IXa. 5 Bilirubin is a free radical scavenger, and as such is considered to be a physiological antioxidant 8,47 ; thus bilirubin serves as an important modulator of immune effector functions. 13 There are at least 2 possible mechanisms by which biliverdin may be exerting its effects on the NF-jB.…”

Relationship Between Bilirubin Concentration, Coronary Endothelial Function, and Inflammatory Stress in Overweight Patients

“…Bilirubin prevents the oxidation of low-density lipoprotein-cholesterol (LDL-C) [1][2][3] , reduces the risk of atherosclerosis and coronary heart disease (CHD) [4][5][6] , tion and impaired fibrinolysis [14][15][16] ; however, the relationship among serum bilirubin, inflammatory markers, and coronary endothelial function remains unclear.…”