Regulation of uridine diphosphate glucuronosyltransferase during the acute-phase response

Abstract

The acute-phase response is associated with profound effects on oxidative drug metabolism. However, the effects on glucuronidation are poorly characterized. The aim of the present study was to determine the role of mediators of the acute-phase response in the regulation of hepatic uridine diphosphate glucuronosyltransferase (UGT) expression. Family 1 and family 2 UGT isoforms were studied in turpentine-injected rats and in primary hepatocyte cultures exposed to tyrone, and/or dexamethasone. In the in vivo model, glucuronidation of p-nitrophenol was unaffected, while testosterone glucuronidation was reduced to 65% of control (P < 0.01). In contrast, the mRNA level of UGT1*1 (which metabolizes..