Xenobiotic receptors in mediating the effect of sepsis on drug metabolism
| Autor: | Chuanzhu Lv, Ling Huang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Oatp2
organic anion transport polypeptide 2 SRC1 steroid receptor coactivator 1 Review Pharmacology Xenobiotic receptors chemistry.chemical_compound AHR aryl hydrocarbon receptor 0302 clinical medicine Glucocorticoid receptor ARNT AHR nuclear translocator PRRs pattern recognition receptors Constitutive androstane receptor GC glucocorticoid GREs glucocorticoid receptor response elements General Pharmacology Toxicology and Pharmaceutics Receptor NOS nitric oxide synthase CYPs cytochrome P450s NF-κB nuclear factor-kappa B 0303 health sciences Pregnane X receptor biology IBD inflammatory bowel disease PCN pregnenolone-16α-carbonitrile PXR pregnane X receptor NR nuclear receptor Inflammatory cytokines CLP cecum ligation and puncture Sult sulfonyl transferase 030220 oncology & carcinogenesis LPS lipopolysaccharide DMEs drug-metabolizing enzymes Drug-metabolizing enzymes Mrp phase III multidrug-resistant protein COX-2 cyclooxygenase 2 IL-1β interleukin-1β HSP90 heat shock protein 90 IRF7 interferon regulatory factor 7 Proinflammatory cytokine Sepsis 03 medical and health sciences PAS Per/ARNT/Sim Drug transporters PKC protein kinase C medicine Ugts UDP-glucuronic transferase 030304 developmental biology Drug metabolism GR glucocorticoid receptor business.industry DREs dioxin response elements IRF3 interferon regulatory factor 3 lcsh:RM1-950 Gsts phase II glutathione S-transferase PLA2 phospholipase A2 STAT3 signal transducers and activators of transcription 3 medicine.disease Aryl hydrocarbon receptor P-gp p-glycoprotein TNF-α tumor necrosis factor lcsh:Therapeutics. Pharmacology chemistry biology.protein Xenobiotic business AP-1 adaptor protein 1 |
| Zdroj: | Acta Pharmaceutica Sinica. B Acta Pharmaceutica Sinica B, Vol 10, Iss 1, Pp 33-41 (2020) |
| ISSN: | 2211-3843 2211-3835 |
| Popis: | Sepsis is an infection-induced systemic inflammatory syndrome. The immune response in sepsis is characterized by the activation of both proinflammatory and anti-inflammatory pathways. When sepsis occurs, the expression and activity of many inflammatory cytokines are markedly affected. Xenobiotic receptors are chemical-sensing transcription factors that play essential roles in the transcriptional regulation of drug-metabolizing enzymes (DMEs). Xenobiotic receptors mediate the functional crosstalk between sepsis and drug metabolism because the inflammatory cytokines released during sepsis can affect the expression and activity of xenobiotic receptors and thus impact the expression and activity of DMEs. Xenobiotic receptors in turn may affect the clinical outcomes of sepsis. This review focuses on the sepsis-induced inflammatory response and xenobiotic receptors such as pregnane X receptor (PXR), aryl hydrocarbon receptor (AHR), glucocorticoid receptor (GR), and constitutive androstane receptor (CAR), DMEs such as CYP1A, CYP2B6, CYP2C9, and CYP3A4, and drug transporters such as p-glycoprotein (P-gp), and multidrug resistance-associated protein (MRPs) that are affected by sepsis. Understanding the xenobiotic receptor-mediated effect of sepsis on drug metabolism will help to improve the safe use of drugs in sepsis patients and the development of new xenobiotic receptor-based therapeutic strategies for sepsis. Graphical abstract The functional crosstalk between sepsis and drug metabolism is mediated by xenobiotic receptors. The inflammatory cytokines released during sepsis can affect the expression and activity of xenobiotic receptors and thus impact the expression and activity of DMEs.Image 1 |
| Databáze: | OpenAIRE |
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