1. Xenobiotic receptors in mediating the effect of sepsis on drug metabolism
- Author
-
Chuanzhu Lv and Ling Huang
- Subjects
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 - Abstract
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
- Published
- 2019