Gadolinium chloride suppresses styrene-induced cytochrome P450s expression in rat liver

  • HIRASAWA Fujiko
    Department of Biochemistry, Akita University School of Medicine
  • KAWAGOE Masami
    Department of Biochemistry, Akita University School of Medicine
  • WANG Jing-Shu
    Department of Biochemistry, Akita University School of Medicine
  • ARANY Szilvia
    Department of Biochemistry, Akita University School of Medicine
  • ZHOU Xiao-Ping
    Department of Biochemistry, Akita University School of Medicine Venture Business Laboratory, Akita University
  • KUMAGAI Ayako
    Department of Biochemistry, Akita University School of Medicine Venture Business Laboratory, Akita University
  • KOIZUMI Yukio
    Department of Biochemistry, Akita University School of Medicine
  • KOYOTA Souichi
    Department of Biochemistry, Akita University School of Medicine
  • SUGIYAMA Toshihiro
    Department of Biochemistry, Akita University School of Medicine

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抄録

To assess the effect of gadolinium (Gd) on the expression of several forms of cytochrome P450 (P450s) and antioxidant enzymes, we treated rats with gadolinium chloride (25 mg as Gd/kg body weight) 4 h after styrene (a multiple P450 inducer) treatment (600 mg/kg). Gd treatment significantly suppressed styrene-inducible cytochrome P4502B1 (CYP2B1), CYP2B2, CYP2E1, and CYP3A2 mRNA expressions to 48.6%, 69.8%, 61.1%, and 38.5%, accompanying with the reduction of proteins expression to 1.42%, 31.2%, 21.1% and 21.1%, respectively, compared with styrene alone treatment. Gd suppressed styrene-inducible CYP1A2 expression, but only at the protein level. On the other hand, styrene treatment caused a decrease in reduced form of glutathione (GSH), as well as increases in lipid peroxide and serum ALT and AST activities, suggesting the occurrence of hepatic damage probably due to styrene-induced oxidative stress in rat liver. Post-treatment of Gd attenuated this styrene-caused hepatic damage. Moreover, mRNA expressions of cellular antioxidant enzymes such as catalase, CuZn-superoxide dismutase (CuZnSOD) and glutathione peroxidase (GPX) were hardly changed by styrene and/or Gd treatment. In summary, Gd suppressed styrene-inducible expression of not only CYP2B1 but also several forms of P450 at both the mRNA and protein levels, along with attenuation of styrene-caused liver damage. These findings suggested that Gd is a chemo-preventive agent against hepatic damage caused by xenobiotics requiring biotransformation.

収録刊行物

  • Biomedical Research

    Biomedical Research 28 (6), 323-330, 2007

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