title: Hepatic effects of tartrazine (E 102) after systemic exposure are independent of oestrogen receptor interactions in the mouse.
abstract: Tartrazine is a food colour that activates the transcriptional function of the human oestrogen receptor alpha in an in vitro cell model. Since oestrogens are cholestatic, we hypothesised tartrazine will cause periportal injury to the liver in vivo. To test this hypothesis, tartrazine was initially administered systemically to mice resulting in a periportal recruitment of inflammatory cells, increased serum alkaline phosphatase activity and mild periportal fibrosis. To determine whether an oestrogenic effect may be a key event in this response, tartrazine, sulphonated metabolites and a food additive contaminant were screened for their ability to interact with murine oestrogen receptors. In all cases, there were no interactions as agonists or antagonists and further, no oestrogenicity was observed with tartrazine in an in vivo uterine growth assay. To examine the relevance of the hepatic effects of tartrazine to its use as a food additive, tartrazine was orally administered to transgenic NF-κB-Luc mice. Pre- and concurrent oral treatment with alcohol was incorporated given its potential to promote gut permeability and hepatic inflammation. Tartrazine alone induced NF- κB activities in the colon and liver but there was no periportal recruitment of inflammatory cells or fibrosis. Tartrazine, its sulphonated metabolites and the contaminant inhibited sulphotransferase activities in murine hepatic S9 extracts. Given the role of sulfotransferases in bile acid excretion, the initiating event giving rise to periportal inflammation and subsequent hepatic pathology through systemic tartrazine exposure is therefore potentially associated an inhibition of bile acid sulphation and excretion and not on oestrogen receptor-mediated transcriptional function. However, these effects were restricted to systemic exposures to tartrazine and did not occur to any significant effect after oral exposure.
authors.affiliation: Institute Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors.forename: Stephanie K
authors.initials: SK
authors.lastname: Meyer
authors.affiliation: Institute Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors.forename: Philip M E
authors.initials: PME
authors.lastname: Probert
authors.affiliation: Institute Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors.forename: Anne F
authors.initials: AF
authors.lastname: Lakey
authors.affiliation: Institute Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Axon
authors.affiliation: Institute Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors.forename: Alistair C
authors.initials: AC
authors.lastname: Leitch
authors.affiliation: Institute Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors.forename: Faith M
authors.initials: FM
authors.lastname: Williams
authors.affiliation: Institute Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Jowsey
authors.affiliation: Institute Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Blain
authors.affiliation: European Food Safety Authority, Via Carlo Magno 1A, 43126 Parma, Italy.
authors.forename: George E N
authors.initials: GEN
authors.lastname: Kass
authors.affiliation: Institute Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom. Electronic address: M.C.Wright@ncl.ac.uk.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Wright
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002460:Cell Line; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D000431:Ethanol / Q000633:toxicity; D005260:Female; D005505:Food Coloring Agents / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008111:Liver Function Tests; D049409:Luciferases, Firefly / Q000235:genetics; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000235:genetics; D013645:Tartrazine / Q000633:toxicity*
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005505:Food Coloring Agents; D016328:NF-kappa B; D000431:Ethanol; D004958:Estradiol; D049409:Luciferases, Firefly; D013645:Tartrazine
keywords: Alcohol; E 102; Food; Liver; NF-κB; oestrogen