Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160-7417, USA.
Toxicol Appl Pharmacol. 2010 Apr 1;244(1):57-65. doi: 10.1016/j.taap.2010.01.013. Epub 2010 Feb 1.
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that positively regulates the basal and inducible expression of a large battery of cytoprotective genes. These gene products include proteins that catalyze reduction reactions (NAD(P)H:quinone oxidoreductase 1, Nqo1), conjugation reactions (glutathione-S-transferases, Gsts and UDP-glucuronosyltransferases, Ugts), as well as the efflux of potentially toxic xenobiotics and xenobiotic conjugates (multidrug resistance-associated proteins, Mrps). The significance of Nrf2 in the liver has been established, as livers of Nrf2-null mice are more susceptible to various oxidative/electrophilic stress-induced pathologies than wild-type mice. In contrast, both pharmacological and genetic models of hepatic Nrf2 activation are protective against oxidative/electrophilic stress. Furthermore, because certain Nrf2-target genes in the liver could affect the distribution, metabolism, and excretion of xenobiotics, the effects of Nrf2 on the kinetics of drugs and other xenobiotics should also be considered, with a special emphasis on metabolism and excretion. Therefore, this review highlights the research that has contributed to the understanding of the importance of Nrf2 in toxicodynamics and toxicokinetics, especially that which pertains to the liver.
核因子红细胞 2 相关因子 2（Nrf2）是一种转录因子，可正向调节大量细胞保护基因的基础和诱导表达。这些基因产物包括催化还原反应的蛋白质（NAD（P）H：醌氧化还原酶 1，Nqo1）、结合反应（谷胱甘肽-S-转移酶、Gsts 和 UDP-葡糖醛酸基转移酶、Ugts），以及潜在有毒的外来物质和外来物质结合物的外排（多药耐药相关蛋白、Mrps）。Nrf2 在肝脏中的重要性已经确立，因为 Nrf2 基因敲除小鼠的肝脏比野生型小鼠更容易受到各种氧化/亲电应激诱导的病理变化的影响。相比之下，肝 Nrf2 激活的药理学和遗传学模型都对氧化/亲电应激具有保护作用。此外，由于肝脏中的某些 Nrf2 靶基因可能会影响外来物质的分布、代谢和排泄，因此还应考虑 Nrf2 对药物和其他外来物质动力学的影响，特别强调代谢和排泄。因此，本文综述了有助于了解 Nrf2 在毒代动力学和毒动学中的重要性的研究，特别是与肝脏相关的研究。
