Regulation of drug-metabolizing enzymes and transporters in inflammation.
Inflammation and infection have long been known to downregulate the activity and expression of cytochrome P450 (CYP) enzymes involved in hepatic drug clearance. This can result in elevated plasma drug levels and increased adverse effects. Recent information on regulation of human CYP enzymes is presented, as are new developments in our understanding of the mechanisms of regulation. Experiments to study the effects of modulating CYP activities on the inflammatory response have yielded possible insights into the physiological consequences, if not the purpose, of the downregulation. Regulation of hepatic flavin monooxygenases, UDP-glucuronosyltransferases, sulfotransferases, glutathione S-transferases, as well as of hepatic transporters during the inflammatory response, exhibits similarities and differences with regulation of CYPs.
Aitken
Alison E
AE
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA. aeaitke@emory.edu
Richardson
Terrilyn A
TA
Morgan
Edward T
ET
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D003580:Cytochromes / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D002352:Carrier Proteins; D003580:Cytochromes; D004364:Pharmaceutical Preparations; D006899:Mixed Function Oxygenases