Bilirubin oxidative metabolites: Novel biomarkers for acute arsenite exposure?

摘要

Human exposure to inorganic arsenic (iAsIII) causes hepatotoxicity. It is known that activation of haem oxygenase-1, a rate limiting enzyme of bilirubin biosynthesis, reduces arsenite-induced hepatotoxicity. Bilirubin, a potent endogenous antioxidant, scavenges radical oxygen species to form oxidative metabolites, such as tripyrroles and propentdyopent. Two novel dipyrrolic metabolites with m/z values 333 and 315 have recently been identified in vitro but their presence in biological samples has yet to be demonstrated. The aim of the present study was to identify the novel dipyrroles in urine of iAsIII treated mice. Acute iAsIII exposure generated transient oxidative stress in the liver, which was associated with temporal induction of haem oxygenase-1, elevation of bilirubin levels, reduction of hepatic lipid peroxidation, and escalation of urinary dipyrroles. The results suggest that bilirubin dipyrrolic metabolites can be used as marker for oxidative stress.