Antioxidant activity of liver growth factor, a bilirubin covalently bound to albumin.
We previously reported that treatment of spontaneously hypertensive rats (SHR) with liver growth factor (LGF), an albumin-bilirubin complex with a covalent bond, reduces blood pressure, improves nitric oxide (NO)-dependent vasodilatation, and exerts vascular antifibrotic actions. Because bilirubin, albumin, and albumin-bound bilirubins have antioxidant properties, we hypothesize that LGF might exert its cardiovascular actions through an antioxidant mechanism. We have tested in vitro the capacity of LGF to scavenge ABTS cation and peroxyl and hydroxyl radicals and to protect vascular NO from degradation by superoxide anion. We have also compared the antioxidant capacity of LGF with that of its molecular components albumin and bilirubin and the reference antioxidant trolox. LGF exhibited antioxidant capacity against all free radicals tested at lower concentrations than albumin, bilirubin, and trolox. LGF, bilirubin, and albumin were also able to protect endothelial NO from superoxide anion degradation in a fashion similar to that of superoxide dismutase or tiron, but at much lower concentrations. These data, together with our previous results in SHR, suggest that LGF might exert its cardiovascular regenerative actions, at least in part, through an antioxidant mechanism and that LGF could be a relevant circulating antioxidant in situations of oxidative stress.
Condezo-Hoyos
Luis
L
Departamento de Fisiología, Universidad Autónoma de Madrid, Spain.
Abderrahim
Fatima
F
Conde
M Victoria
MV
Susín
Cristina
C
Díaz-Gil
Juan J
JJ
González
M Carmen
MC
Arribas
Silvia M
SM
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D052160:Benzothiazoles / Q000032:analysis; D001663:Bilirubin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D001795:Blood Pressure Determination; D002339:Carotid Arteries / Q000473:pathology; D002839:Chromans / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D005355:Fibrosis / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control; D017665:Hydroxyl Radical / Q000032:analysis; D006973:Hypertension / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D009569:Nitric Oxide / Q000032:analysis; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010545:Peroxides / Q000032:analysis; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism*; D000075462:Serum Albumin, Human; D013451:Sulfonic Acids / Q000032:analysis
D000975:Antioxidants; D052160:Benzothiazoles; D002839:Chromans; D010545:Peroxides; D012709:Serum Albumin; D013451:Sulfonic Acids; C053498:albumin-bilirubin complex; D012710:Serum Albumin, Bovine; C002502:2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid; C049375:perhydroxyl radical; D009569:Nitric Oxide; D017665:Hydroxyl Radical; D001663:Bilirubin; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D000075462:Serum Albumin, Human