Effect of Hemodialysis on Hepatic Cytochrome P450 Functional Expression

DOI Web Site 被引用文献6件 参考文献38件
  • Michaud Josée
    Service de Néphrologie et Centre de Recherche Guy-Bernier, Hôpital Maisonneuve-Rosemont, Canada Département de Pharmacologie, Université de Montréal, Canada
  • Nolin Thomas D.
    Division of Nephrology and Transplantation, Department of Medicine, Maine Medical Center, USA Center for Clinical and Translational Research, Maine Medical Center Research Institute, USA
  • Naud Judith
    Service de Néphrologie et Centre de Recherche Guy-Bernier, Hôpital Maisonneuve-Rosemont, Canada Département de Pharmacologie, Université de Montréal, Canada
  • Dani Mélina
    Service de Néphrologie et Centre de Recherche Guy-Bernier, Hôpital Maisonneuve-Rosemont, Canada Département de Pharmacologie, Université de Montréal, Canada
  • Leblond Francois A.
    Division of Nephrology and Transplantation, Department of Medicine, Maine Medical Center, USA Center for Clinical and Translational Research, Maine Medical Center Research Institute, USA
  • Lafrance Jean-Philippe
    Service de Néphrologie et Centre de Recherche Guy-Bernier, Hôpital Maisonneuve-Rosemont, Canada
  • Himmelfarb Jonathan
    Division of Nephrology and Transplantation, Department of Medicine, Maine Medical Center, USA Center for Clinical and Translational Research, Maine Medical Center Research Institute, USA
  • Pichette Vincent
    Service de Néphrologie et Centre de Recherche Guy-Bernier, Hôpital Maisonneuve-Rosemont, Canada Département de Pharmacologie, Université de Montréal, Canada

書誌事項

公開日
2008
DOI
  • 10.1254/jphs.08042fp
公開者
公益社団法人 日本薬理学会

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説明

Cytochrome P450 (CYP) functional expression is reduced in uremia and normalized after restoration of kidney function via transplantation. The aim of this study was to evaluate the effect of conventional hemodialysis on the functional expression of CYP1A, 2C, and 3A. We also investigated the role of nuclear factor-κB (NF-κB) in CYP regulation during uremia. Primary cultures of normal rat hepatocytes were incubated with serum obtained from end-stage renal disease patients pre- and post-hemodialysis and healthy control subjects, in the presence and absence of the NF-κB inhibitor andrographolide. Uremic pre-hemodialysis serum caused significant reductions (P<0.01) in CYP1A (44%), 2C (27%), and 3A (35%) protein expression compared to control serum, while dialyzed serum (i.e., obtained immediately post-hemodialysis) had no effect. CYP1A2, 2C11, and 3A2 mRNA expression, as well as CYP3A activity, were similarly impacted by uremic serum and were improved to >80% of control values after hemodialysis. NF-κB inhibition nearly eliminated the effect of uremic serum on CYP functional expression. This is the first study to demonstrate that conventional hemodialysis acutely improves altered CYP functional expression observed in rat hepatocytes incubated with uremic human serum.<br>

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