Isothiocyanates induce UGT1A1 in humanized UGT1 mice in a CAR dependent fashion that is highly dependent upon oxidative stress

摘要: Isothiocyanates, such as phenethyl isothiocyanate (PEITC), are formed following the consumption of cruciferous vegetables and generate reactive oxygen species (ROS) that lead to induction cytoprotective genes UDP-glucuronosyltransferases (UGTs). The ROS activates Nrf2-Keap 1 pathway leading through antioxidant response elements (AREs). UGT1A1, sole enzyme responsible for metabolism bilirubin, can be induced activation Nrf2. When neonatal humanized UGT1 (hUGT1) mice, which exhibit severe levels total serum bilirubin (TSB) because a developmental delay in expression UGT1A1 gene, were treated with PEITC, TSB reduced. Liver intestinal induced, along murine CYP2B10, consensus CAR target gene. In both adult hUGT1/Car-/- PEITC was unable induce CYP2B10. A similar result observed analysis liver. However, still reduced mice UGT1A1. oxidative stress blocked by exposing N-acetylcysteine, liver CYP2B10 prevented. Thus, new findings this report link an important role is dependent upon stress.