[Bilirubin as an endogenous intermediary in the activation of CYP1A1 expression upon exposure to ultrasound].

Abstract

The induction of cytochrome P4501A1 (CYP1A1) enzyme activity reflects the increased ligand-dependent transcriptional activity of the cognate CYP1A1 gene. The list of ligands includes various xenobotics such as polycyclic and halogenated aromatic hydrocarbons. Until recently, similar role for endogenous compounds was unknown. In the present study the ability of the endogenous heme metabolite, bilirubin, to regulate CYP1A1 activity was examined. The following parameters were investigated: expression of CYP1A1 in rat liver at a level mRNA, protein and functional activity under at the experimental rising of blood bilirubin level. The influence of local ultrasound contact treatment of rats hepatic area in vivo (the intensity 0.4 W/cm2 and duration time of 10 minutes) on blood unconjugated bilirubin concentration and parameters of CYP1A1 transcriptional activity was also investigated. The ultrasound contact action on rat hepatic are increased blood unconjugated bilirubin concentration. The rise of bilirubin levels of in rat blood after intravenous administration of bilirubin as well as after ultrasound treatment was accompanied by increased mRNA CYP1A1, protein and functional activity of CYP1A1. The comparison of these data with that of time-dependent changes of parameters of CYP1A1 transcriptional activity under ultrasound action and experimental rising of blood bilirubin level suggest that induces CYP1A1 and may be an intermediate in the activation of CYP1A1 expression under ultrasound action.