ArticlePloS one2012
Effect of graded Nrf2 activation on phase-I and -II drug metabolizing enzymes and transporters in mouse liver.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
81 citing papers in PubMed, 144 citations in OpenAlex.
- Unraveling the role of deuterium in cancer: mechanisms, detection techniques, and therapeutic potential.Molecular diversity · 2026Review
- Review
- Sex-based differences in the NRF2 oxidative stress response: Implications for precision therapeutics.Redox biology · 2026Review
- Three-Month Administration of PB125 Modifies Histopathology, Redox Homeostasis, and Mobility in the Hartley Guinea Pig Model of Primary Osteoarthritis.Antioxidants (Basel, Switzerland) · 2026Article
- Article
- Distinct roles for the thioredoxin and glutathione antioxidant systems in Nrf2-Mediated lung tumor initiation and progression.Redox biology · 2025Article
- Review
- Kefir enhances stress resilience and mitigates PTSD-related behavioral and hematological changes in mice.Frontiers in physiology · 2025Article
- Sleep and Oxidative Stress: Current Perspectives on the Role of NRF2.Cellular and molecular neurobiology · 2024Review
- Microglia at the blood brain barrier in health and disease.Frontiers in cellular neuroscience · 2024Review
- Emerging Drug Delivery Vectors: Engineering of Plant-Derived Nanovesicles and Their Applications in Biomedicine.International journal of nanomedicine · 2024Review
- Transcription Factor NRF2 in Shaping Myeloid Cell Differentiation and Function.Advances in experimental medicine and biology · 2024Review
- Reactive Oxygen Species and NRF2 Signaling, Friends or Foes in Cancer?Biomolecules · 2023Review
- Nrf2Frontiers in genetics · 2023Article
- Potential oxidative stress related targets of mitochondria-focused therapy of PTSD.Frontiers in physiology · 2023Review
- Therapeutic Effects of Green Tea Polyphenol (‒)-Epigallocatechin-3-Gallate (EGCG) in Relation to Molecular Pathways Controlling Inflammation, Oxidative Stress, and Apoptosis.International journal of molecular sciences · 2022Review
- Blockage of Nrf2 and autophagy by L-selenocystine induces selective death in Nrf2-addicted colorectal cancer cells through p62-Keap-1-Nrf2 axis.Cell death & disease · 2022Article
- Article
- Dynamic modeling of Nrf2 pathway activation in liver cells after toxicant exposure.Scientific reports · 2022Article
- Sulforaphane Exerts Beneficial Immunomodulatory Effects on Liver TissueFrontiers in immunology · 2022Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that induces a battery of cytoprotective genes in response to oxidative/electrophilic stress. Kelch-like ECH associating protein 1 (Keap1) sequesters Nrf2 in the cytosol. The purpose of this study was to investigate the role of Nrf2 in regulating the mRNA of genes encoding drug metabolizing enzymes and xenobiotic transporters. Microarray analysis was performed in livers of Nrf2-null, wild-type, Keap1-knockdown mice with increased Nrf2 activation, and Keap1-hepatocyte knockout mice with maximum Nrf2 activation. In general, Nrf2 did not have a marked effect on uptake transporters, but the mRNAs of organic anion transporting polypeptide 1a1, sodium taurocholate cotransporting polypeptide, and organic anion transporter 2 were decreased with Nrf2 activation. The effect of Nrf2 on cytochrome P450 (Cyp) genes was minimal, with only Cyp2a5, Cyp2c50, Cyp2c54, and Cyp2g1 increased, and Cyp2u1 decreased with enhanced Nrf2 activation. However, Nrf2 increased mRNA of many other phase-I enzymes, such as aldo-keto reductases, carbonyl reductases, and aldehyde dehydrogenase 1. Many genes involved in phase-II drug metabolism were induced by Nrf2, including glutathione S-transferases, UDP- glucuronosyltransferases, and UDP-glucuronic acid synthesis enzymes. Efflux transporters, such as multidrug resistance-associated proteins, breast cancer resistant protein, as well as ATP-binding cassette g5 and g8 were induced by Nrf2. In conclusion, Nrf2 markedly alters hepatic mRNA of a large number of drug metabolizing enzymes and xenobiotic transporters, and thus Nrf2 plays a central role in xenobiotic metabolism and detoxification.
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