Urinary excretion of bilirubin oxidative metabolites in arsenite-treated mice.

Human exposure to inorganic arsenic (iAsIII), a potent oxidative stressor, causes liver injuries, which can lead to cancer. It is known that induction of haem oxygenase-1 (HMOX1) reduces arsenite-induced cytotoxicity in the liver. In a two-step reaction HMOX1 generates BR from haem and BR, in turn is oxidised to its oxidative metabolites by radical oxygen species (ROS). Bilirubin oxidative metabolites (BOMs), such as tripyrroles and propentdyopent have been identified and measured in rat and human urine. Additionally, two novel dipyrroles (with m/z values 333 and 315) have recently been identified in vitro (Abu-Bakar et al. (2011). Toxicol. Appl. Pharmacol., 257, 14-22) 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 control and iAsIII treated mice. Acute iAsIII exposure generated transient oxidative stress in the liver, which associated with temporal induction of hepatic HMOX1, the rate-limiting enzyme of BR biosynthesis. The increase in the total BR levels was modest compared to the strong induction of HMOX1. Additionally, urinary dipyrroles (m/z values 333 and 315) escalated after iAsIII exposure. The results suggest that dipyrrolic BOMs can be used as marker for oxidative stress. [ABSTRACT FROM AUTHOR]