Albumin-bound bilirubins protect human ventricular myocytes against oxyradical damage

Abstract

Synthetic delta-bilirubin (i.e., bilirubin that is covalently bonded to albumin) and, to a lesser extent, bilirubin that is physically adsorbed to albumin substantially prolonged the survival of human ventricular myocytes against in situ generated oxyradicals. This cytoprotection, manifested at micromolar concentrations of either form of bilirubin, surpasses those given by unconjugated bilirubin alone, by equimolar levels of albumin (which has some cytoprotective activity), by known antioxidants ascorbate, mannitol, or Trolox, and by oxyradical scavenging enzymes superoxide dismutase (24,200 IU/L) plus catalase (92,000 IU/L) on the same cells. Our human cell-based data provide the first direct evidence that albumin-bound bilirubins, especially delta bilirubin, are potent circulating cytoprotectors. The latter may be important in defending, among others, the myocardium, which is much less equipped in antioxidant defences than for example the liver or intestines.