Xenobiotic receptors in mediating the effect of sepsis on drug metabolism.
10.1016/j.apsb.2019.12.003
- Author:
Chuanzhu LV
1
;
Ling HUANG
2
Author Information
1. Department of Emergency, Hainan Clinical Research Center for Acute and Critical Diseases, The Second Affiliated Hospital of Hainan Medical University, Haikou 570300, China.
2. Research Center for Drug Safety Evaluation of Hainan Province, Hainan Medical University, Haikou 571101, China.
- Publication Type:Journal Article
- Keywords:
AHR, aryl hydrocarbon receptor;
AP-1, adaptor protein 1;
ARNT, AHR nuclear translocator;
CLP, cecum ligation and puncture;
COX-2, cyclooxygenase 2;
CYPs, cytochrome P450s;
DMEs, drug-metabolizing enzymes;
DREs, dioxin response elements;
Drug metabolism;
Drug transporters;
Drug-metabolizing enzymes;
GC, glucocorticoid;
GR, glucocorticoid receptor;
GREs, glucocorticoid receptor response elements;
Gsts, phase II glutathione S-transferase;
HSP90, heat shock protein 90;
IBD, inflammatory bowel disease;
IL-1β, interleukin-1β;
IRF3, interferon regulatory factor 3;
IRF7, interferon regulatory factor 7;
Inflammatory cytokines;
LPS, lipopolysaccharide;
Mrp, phase III multidrug-resistant protein;
NF-κB, nuclear factor-kappa B;
NOS, nitric oxide synthase;
NR, nuclear receptor;
Oatp2, organic anion transport polypeptide 2;
P-gp, p-glycoprotein;
PAS, Per/ARNT/Sim;
PCN, pregnenolone-16α-carbonitrile;
PKC, protein kinase C;
PLA2, phospholipase A2;
PRRs, pattern recognition receptors;
PXR, pregnane X receptor;
SRC1, steroid receptor coactivator 1;
STAT3, signal transducers and activators of transcription 3;
Sepsis;
Sult, sulfonyl transferase;
TNF-α, tumor necrosis factor;
Ugts, UDP-glucuronic transferase;
Xenobiotic receptors
- From:
Acta Pharmaceutica Sinica B
2020;10(1):33-41
- CountryChina
- Language:English
-
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.
