title: Expression of hepatic cytochrome P450 in a mouse model of ulcerative colitis changes with pathological conditions.
abstract: OBJECTIVE
  The expression levels of cytochrome P450 (CYP) in the liver were analyzed over time in dextran sulfate sodium (DSS)-induced ulcerative colitis mouse model, from the initial active stage to the remission stage, to investigate the relationship between the changes in pathological conditions and CYP expression levels.
  
  
  METHODS
  DSS solution was given to mice for 10 days, after which water without DSS was provided for 40 days. Pathological conditions and CYP expression levels were examined over time. The mechanism for variation in CYP expression was also analyzed.
  
  
  RESULTS
  The mRNA expression levels of CYP (CYP3A11, CYP1A2, CYP2C29, CYP2D9, and CYP2E1) decreased as pathological conditions worsened and reached their lowest levels on day 10 of DSS treatment. Pathological conditions improved following the discontinuation of DSS, and CYP expression levels normalized by day 50. Blood lipopolysaccharide levels, the hepatic expression of inflammatory cytokines, and the nuclear translocation of pregnane X receptor and constitutive androstane receptor in the liver exhibited patterns similar to the observed variations in CYP expression levels.
  
  
  CONCLUSIONS
  The capacity for metabolizing drugs that are substrates of CYP decreases during the active stage of ulcerative colitis but subsequently improves during the remission stage. This decrease in CYP expression was likely caused by the observed reduction in the levels of nuclearly localized pregnane X receptor and constitutive androstane receptor, and the increase in the production of inflammatory cytokines triggered by lipopolysaccharides.
authors: Department of Clinical Pharmacokinetics, Hoshi University, Tokyo, Japan.
authors: Yoshiki
authors: Y
authors: Kusunoki
authors: Department of Clinical Pharmacokinetics, Hoshi University, Tokyo, Japan.
authors: Nobutomo
authors: N
authors: Ikarashi
authors: Department of Clinical Pharmacokinetics, Hoshi University, Tokyo, Japan.
authors: Shogo
authors: S
authors: Matsuda
authors: Department of Clinical Pharmacokinetics, Hoshi University, Tokyo, Japan.
authors: Yoshimi
authors: Y
authors: Matsukawa
authors: Department of Clinical Pharmacokinetics, Hoshi University, Tokyo, Japan.
authors: Satoshi
authors: S
authors: Kitaoka
authors: Department of Clinical Pharmacokinetics, Hoshi University, Tokyo, Japan.
authors: Risako
authors: R
authors: Kon
authors: Department of Clinical Pharmacokinetics, Hoshi University, Tokyo, Japan.
authors: Masataka
authors: M
authors: Tajima
authors: Division of Applied Pharmaceutical Education and Research, Hoshi University, Tokyo, Japan.
authors: Nobuyuki
authors: N
authors: Wakui
authors: Department of Clinical Pharmacokinetics, Hoshi University, Tokyo, Japan.
authors: Wataru
authors: W
authors: Ochiai
authors: Division of Applied Pharmaceutical Education and Research, Hoshi University, Tokyo, Japan.
authors: Yoshiaki
authors: Y
authors: Machida
authors: Department of Clinical Pharmacokinetics, Hoshi University, Tokyo, Japan.
authors: Kiyoshi
authors: K
authors: Sugiyama
mesh_terms: D000818:Animals; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D000090702:Constitutive Androstane Receptor; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D015870:Gene Expression / Q000235:genetics*; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D008813:Mice, Inbred ICR; D000077297:Pregnane X Receptor; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism
chemical_list: D000090702:Constitutive Androstane Receptor; D016207:Cytokines; D018836:Inflammation Mediators; D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D003577:Cytochrome P-450 Enzyme System; D016264:Dextran Sulfate
keywords: cytochrome P450; inflammatory cytokine; lipopolysaccharide; pregnane X receptor; ulcerative colitis