title: Regulation of drug-metabolizing enzymes by local and systemic liver injuries.
abstract: BACKGROUND
  Drug metabolism and disposition are critical in maintaining the chemical and functional homeostasis of xenobiotics/drugs and endobiotics. The liver plays an essential role in drug metabolism and disposition due to its abundant expression of drug-metabolizing enzymes (DMEs) and transporters. There is growing evidence to suggest that many hepatic and systemic diseases can affect drug metabolism and disposition by regulating the expression and/or activity of DMEs and transporters in the liver.
  
  
  METHODS
  This review focuses on the recent progress on the regulation of DMEs by local and systemic liver injuries. Liver ischemia and reperfusion (I/R) and sepsis are used as examples of local and systemic injury, respectively. The reciprocal effect of the expression and activity of DMEs on animals' sensitivity to local and systemic liver injuries is also discussed.
  
  
  CONCLUSIONS
  Local and systemic liver injuries have a major effect on the expression and activity of DMEs in the liver. Understanding the disease effect on DMEs is clinically important due to the concern of disease-drug interactions. Future studies are necessary to understand the mechanism by which liver injury regulates DMEs. Human studies are also urgently needed in order to determine whether the results in animals can be replicated in human patients.
authors.affiliation: a Center for Pharmacogenetics and Department of Pharmaceutical Sciences , University of Pittsburgh , Pittsburgh , PA , USA.|b Department of Pathology , Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: a Center for Pharmacogenetics and Department of Pharmaceutical Sciences , University of Pittsburgh , Pittsburgh , PA , USA.|c Institute of Clinical Pharmacology , Sun Yat-Sen University , Guangzhou , China.
authors.forename: Bingfang
authors.initials: B
authors.lastname: Hu
authors.affiliation: a Center for Pharmacogenetics and Department of Pharmaceutical Sciences , University of Pittsburgh , Pittsburgh , PA , USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xie
authors.affiliation: d Department of Surgery , University of Pittsburgh , Pittsburgh , PA , USA.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Billiar
authors.affiliation: d Department of Surgery , University of Pittsburgh , Pittsburgh , PA , USA.
authors.forename: Jason L
authors.initials: JL
authors.lastname: Sperry
authors.affiliation: c Institute of Clinical Pharmacology , Sun Yat-Sen University , Guangzhou , China.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: a Center for Pharmacogenetics and Department of Pharmaceutical Sciences , University of Pittsburgh , Pittsburgh , PA , USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Xie
mesh_terms: D000818:Animals; D004798:Enzymes / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008107:Liver Diseases / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D026901:Membrane Transport Proteins / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D013045:Species Specificity; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D004798:Enzymes; D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations; D015262:Xenobiotics
keywords: Animal models; drug-metabolizing enzyme; ischemia and reperfusion; sepsis