title: α-Tocopherol injections in rats up-regulate hepatic ABC transporters, but not cytochrome P450 enzymes.
abstract: The role of hepatic xenobiotic regulatory mechanisms in modulating hepatic α-tocopherol concentrations during excess vitamin E administration remains unclear. We hypothesized that increased hepatic α-tocopherol would cause a marked xenobiotic response. Thus, we assessed cytochrome P450 oxidation systems (phase I), conjugation systems (phase II), and transporters (phase III) after daily α-tocopherol injections (100mg/kg body wt) for up to 9days in rats. α-Tocopherol injections increased hepatic α-tocopherol concentrations nearly 20-fold, along with a 10-fold increase in the hepatic α-tocopherol metabolites α-CEHC and α-CMBHC. Expression of phase I (CYP3A2, CYP3A1, CYP2B2) and phase II (SULT2A1) proteins and/or mRNAs was variably affected by α-tocopherol injections; however, expression of phase III transporter genes was consistently changed by α-tocopherol. Two liver efflux transporter genes, ABCB1b and ABCG2, were up-regulated after α-tocopherol injections, whereas OATP, a liver influx transporter, was down-regulated. Thus, an overload of hepatic α-tocopherol increases its own metabolism and increases expression of genes of transporters that are postulated to lead to increased excretion of both vitamin E and its metabolites.
authors.affiliation: Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA. maret.traber@oregonstate.edu
authors.forename: Maret G
authors.initials: MG
authors.lastname: Traber
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Labut
authors.forename: Scott W
authors.initials: SW
authors.lastname: Leonard
authors.forename: Katie M
authors.initials: KM
authors.lastname: Lebold
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D024502:alpha-Tocopherol / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D003577:Cytochrome P-450 Enzyme System; D024502:alpha-Tocopherol