title: Gadolinium chloride suppresses styrene-induced cytochrome P450s expression in rat liver.
abstract: 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.
authors.affiliation: Department of Biochemistry, Akita University School of Medicine, Akita 010-8543, Japan.
authors.forename: Fujiko
authors.initials: F
authors.lastname: Hirasawa
authors.forename: Masami
authors.initials: M
authors.lastname: Kawagoe
authors.forename: Jing-Shu
authors.initials: JS
authors.lastname: Wang
authors.forename: Szilvia
authors.initials: S
authors.lastname: Arany
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Zhou
authors.forename: Ayako
authors.initials: A
authors.lastname: Kumagai
authors.forename: Yukio
authors.initials: Y
authors.lastname: Koizumi
authors.forename: Souichi
authors.initials: S
authors.lastname: Koyota
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sugiyama
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction; D005682:Gadolinium / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000633:toxicity*; D020058:Styrene / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D012997:Solvents; D020058:Styrene; D003577:Cytochrome P-450 Enzyme System; D005682:Gadolinium; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; C038958:gadolinium chloride