Elevated plasma levels of bilirubin in patients with neurotrauma reflect its pathophysiological role in free radical scavenging

Bilirubin, a powerful endogenous antioxidant, is one of the catabolites of heme oxygenases (HOs). In this study, the plasma bilirubin concentration was measured to establish bilirubin kinesis after traumatic brain injury (TBI). Furthermore, in in vitro studies, the free radical scavenging activity and antioxidant potency of bilirubin was also investigated at various concentrations, including physiological ones. Indirect plasma bilirubin was measured in 25 patients on days 1, 2, 3 and 4 after presentation with TBI. The ability of bilirubin to scavenge the hydroxyl (OH·) and 1,1-diphenyl-2-picrylhyrazyl (DPPH) radicals, and its antioxidant potency, were also analyzed using electron spin resonance (ESR) and the bioantioxidant power (BAP) methods, respectively. Plasma bilirubin levels were significantly higher on days 2, 3 and 4 than on patient admission (day 1; p<0.05). ESR and BAP results revealed that bilirubin has direct OH· and DPPH radical scavenging activities and potent antioxidant effects in vitro at physiological concentrations. These data indicate that physiological concentrations of bilirubin have antioxidant properties and that it constitutes one of the biological defense mechanisms in neurotrauma patients.