Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 10 No. 6 November 22, 2023 p.265-277
Original Article
Differential expression of Cytochrome P450 1A2 in simple fatty liver and steatohepatitis
  • Toshiyuki Higuchi (Division of Pharmaceutical Health Biosciences, Nihon Pharmaceutical University / higuchi@nichiyaku.ac.jp)
Azusa Kawashima 1) , Naoto Uramaru 1) , Toshiyasu Mikuma 2) , Makoto Osabe 1) , Toshiyuki Higuchi 1)
1) Division of Pharmaceutical Health Biosciences, Nihon Pharmaceutical University , 2) Division of Physical and Analytical Sciences, Nihon Pharmaceutical University
Keywords: Cytochrome P450s, Non-alcoholic fatty liver disease, Non-alcoholic fatty liver, Non-alcoholic steatohepatitis, Lipid accumulation, Drug interaction
Abstracts

Clarifying the cytochrome P450s (CYPs) changes in non-alcoholic fatty liver disease (NAFLD) is important for optimizing drug therapy. This study compared the expression of CYP isoforms in rat models of nonalcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). An NAFL model without tissue damage or inflammation was established by feeding rats a high-fat diet (HFD) for a relatively short period of 4 weeks. Feeding rats with a methionine-choline-deficient diet (MCDD) for 4 weeks produced steatohepatitis-like NASH. Here, the mRNA and protein expression levels of several CYP enzymes in NAFL and NASH models were compared with those in rats fed a control diet (CD). CYP1A2 expression and activity were upregulated in the NAFL model and downregulated in the NASH model, suggesting a reversal of CYP1A2 expression between NAFL and NASH. Differential expression of CYP1A2 in the NAFL and NASH models was observed in primary rat hepatocytes. These findings suggest that CYP1A2 expression/activity vary from the early stages of NAFL to NASH and that monitoring the pharmacokinetics of CYP1A2-metabolized drugs in humans with NAFL and NASH is necessary.