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Chuanzhu Lv, Ling Huang. Xenobiotic receptors in mediating the effect of sepsis on drug metabolism[J]. Acta Pharmaceutica Sinica B, 2020, 10(1): 33-41

Xenobiotic receptors in mediating the effect of sepsis on drug metabolism
Chuanzhu Lva,b,c,f, Ling Huangd,e,f
a Department of Emergency, Hainan Clinical Research Center for Acute and Critical Diseases, The Second Affiliated Hospital of Hainan Medical University, Haikou 570300, China;
b Emergency and Trauma College, Hainan Medical University, Haikou 571101, China;
c Research Unit of Island Emergency Medicine, Chinese Academy of Medical Sciences, Hainan Medical University, Haikou 571101, China;
d Research Center for Drug Safety Evaluation of Hainan Province, Hainan Medical University, Haikou 571101, China;
e Hainan Province Key Laboratory for Drug Preclinical Study of Pharmacology and Toxicology Research, Hainan Medical University, Haikou 571101, China;
f Key Laboratory of Emergency and Trauma of Ministry of Education, Hainan Medical University, Haikou 571101, China
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.
Key words:    Sepsis    Inflammatory cytokines    Xenobiotic receptors    Drug metabolism    Drug-metabolizing enzymes    Drug transporters   
Received: 2019-07-18     Revised: 2019-09-28
DOI: 10.1016/j.apsb.2019.12.003
Funds: This work was supported by grants from the National Natural Science Foundation of China (8140130969and 8176130232), and Hainan Provincial Science and Technology Major Project (ZDKJ201804, China).
Corresponding author: Chuanzhu Lv, Ling Huang     Email:lvchuanzhu677@126.com;puer6@163.com
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