Nrf2 is essential for the chemopreventive efficacy of oltipraz against urinary bladder carcinogenesis.

摘要: The induction of phase 2 detoxifying enzymes, such as UDP-glucuronosyltransferases (UGTs), in response to an array naturally occurring and synthetic agents, oltipraz (4-methyl-5-[2-pyrazinyl]-1,2-dithiole-3-thione), provides effective means protection against a variety carcinogens. Transcription factor Nrf2 is essential regulator the inducible expression enzyme genes by chemopreventive agents. In this study, we investigated Nrf2-deficient mice susceptibility urinary bladder-specific carcinogen N-nitrosobutyl(4-hydroxybutyl)amine (BBN) efficacy oltipraz. incidence bladder carcinoma BBN was significantly higher Nrf2-/- than wild-type mice; invasive found 24.0 38.5% mice, respectively. Oltipraz induced enzymes responsible for detoxification liver Nrf2-dependent manner. As expected, therefore, decreased but had little effect mice. mouse liver, glucuronidation concentration N-nitrosobutyl(3-carboxypropyl)amine, proximate BBN. Importantly, suppress UGT1A specifically bladder. This suppression counteracted not These results show that its downstream target are detoxification. Furthermore, prevents carcinogenesis enhancing