ArticlePharmaceutical research2011
The role of constitutive androstane receptor in oxazaphosphorine-mediated induction of drug-metabolizing enzymes in human hepatocytes.
Article in Pharmaceutical research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- Genetic markers in CYP2C19 and CYP2B6 for prediction of cyclophosphamide's 4-hydroxylation, efficacy and side effects in Chinese patients with systemic lupus erythematosus.British journal of clinical pharmacology · 2016Trial
- Microphysiological Drug-Testing Platform for Identifying Responses to Prodrug Treatment in Primary Leukemia.Advanced healthcare materials · 2023Article
- Pharmacometabonomic association of cyclophosphamide 4-hydroxylation in hematopoietic cell transplant recipients.Clinical and translational science · 2022Article
- Pharmacokinetic parameters of ifosfamide in mouse pre-administered with grapefruit juice or naringin.Scientific reports · 2019Article
- Sulforaphane Alters β-Naphthoflavone-Induced Changes in Activity and Expression of Drug-Metabolizing Enzymes in Rat Hepatocytes.Molecules (Basel, Switzerland) · 2017Article
- Activation of the Constitutive Androstane Receptor Increases the Therapeutic Index of CHOP in Lymphoma Treatment.Molecular cancer therapeutics · 2016Article
- Small-molecule modulators of the constitutive androstane receptor.Expert opinion on drug metabolism & toxicology · 2015Review
- PharmGKB summary: ifosfamide pathways, pharmacokinetics and pharmacodynamics.Pharmacogenetics and genomics · 2014Article
- Metformin represses drug-induced expression of CYP2B6 by modulating the constitutive androstane receptor signaling.Molecular pharmacology · 2014Article
- Article
- Oxazaphosphorine bioactivation and detoxification The role of xenobiotic receptors.Acta pharmaceutica Sinica. B · 2012Article
- An insulin-like growth factor 1 receptor inhibitor induces CYP3A4 expression through a pregnane X receptor-independent, noncanonical constitutive androstane receptor-related mechanism.The Journal of pharmacology and experimental therapeutics · 2012Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo investigate the roles of the constitutive androstane receptor (CAR) in cyclophosphamide (CPA)- and ifosfamide (IFO)-mediated induction of hepatic drug-metabolizing enzymes (DME).
methodsInduction of DMEs was evaluated using real-time RT-PCR and Western blotting analysis in human primary hepatocyte (HPH) cultures. Activation of CAR, pregnane X receptor (PXR), and aryl hydrocarbon receptor by CPA and IFO was assessed in cell-based reporter assays in HepG2 cells and/or nuclear translocation assays in HPHs.
resultsCYP2B6 reporter activity was significantly enhanced by CPA and IFO in HepG2 cells co-transfected with CYP2B6 reporter plasmid and a chemical-responsive human CAR variant (CAR1 + A) construct. Real-time RT-PCR and Western blotting analysis in HPHs showed that both CPA and IFO induced the expressions of CYP2B6 and CYP3A4. Notably, treatment of HPHs with CPA but not IFO resulted in significant nuclear accumulation of CAR, which represents the initial step of CAR activation. Further studies in HPHs demonstrated that selective inhibition of PXR by sulforaphane preferentially repressed IFO- over CPA-mediated induction of CYP2B6.
conclusionThese results provide novel insights into the differential roles of CAR in the regulation of CPA- and IFO-induced DME expression and potential drug-drug interactions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.