NDLI: -Tocopherol injections in rats up-regulate hepatic ABC transporters, but not cytochrome P450 enzymes.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Traber, Maret G. Labut, Edwin M. Leonard, Scott W. Lebold, Katie M.
Description	Country affiliation: United States Author Affiliation: Traber MG ( Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA. maret.traber@oregonstate.edu)
Abstract	The role of hepatic xenobiotic regulatory mechanisms in modulating hepatic -tocopherol concentrations during excess vitamin E administration remains unclear. We hypothesized that increased hepatic -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 -tocopherol injections (100mg/kg body wt) for up to 9days in rats. -Tocopherol injections increased hepatic -tocopherol concentrations nearly 20-fold, along with a 10-fold increase in the hepatic -tocopherol metabolites -CEHC and -CMBHC. Expression of phase I (CYP3A2, CYP3A1, CYP2B2) and phase II (SULT2A1) proteins and/or mRNAs was variably affected by -tocopherol injections; however, expression of phase III transporter genes was consistently changed by -tocopherol. Two liver efflux transporter genes, ABCB1b and ABCG2, were up-regulated after -tocopherol injections, whereas OATP, a liver influx transporter, was down-regulated. Thus, an overload of hepatic -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.
File Format	HTM / HTML
ISSN	08915849
e-ISSN	18734596
DOI	10.1016/j.freeradbiomed.2011.08.033
Journal	Free Radical Biology and Medicine
Issue Number	11
Volume Number	51
Language	English
Publisher	Elsevier
Publisher Date	2011-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Free radicals biology Atp-binding Cassette Transporters Metabolism Cytochrome P-450 Enzyme System Hepatocytes Alpha-tocopherol Administration & Dosage Animals Cytology Drug Effects Rats, Sprague-dawley Research Support, N.i.h., Extramural
Content Type	Text
Resource Type	Article
Subject	Physiology (medical) Biochemistry

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