Fundamental Toxicological Sciences
Online ISSN : 2189-115X
ISSN-L : 2189-115X
Original Article
Differential expression of Cytochrome P450 1A2 in simple fatty liver and steatohepatitis
Azusa KawashimaNaoto UramaruToshiyasu MikumaMakoto OsabeToshiyuki Higuchi
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2023 Volume 10 Issue 6 Pages 265-277


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.

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© 2023 The Japanese Society of Toxicology
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