4.5 Article

Effects of phthalate ester derivatives including oxidized metabolites on coactivator recruiting by PPARα and PPARγ

期刊

TOXICOLOGY IN VITRO
卷 22, 期 6, 页码 1534-1538

出版社

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2008.05.010

关键词

phthalate ester; DEHP; MEHP; oxidized metabolite; PPAR; peroxisome proliferator; coactivator

资金

  1. Research Institute of Meijo University
  2. Scientific Frontier Research Project
  3. Ministry of Education, Culture, Sports, Science and Technology of Japan

向作者/读者索取更多资源

Phthalate esters (PEs), a group of environmental chemicals, affect biological systems via endocrine and lipid metabolism modulations. These effects are believed to be mediated in part by peroxisome proliferator-activated receptors (PPARs). Evaluations of PE activities as ligands toward PPARs have been investigated in many studies on their primary metabolites, monoesters. However, the activities of various other metabolites, including oxidized derivatives, remain to be determined. Here, we have evaluated the PPAR ligand activities of these PE derivatives by in vitro coactivator recruiting assay. Mono(2-ethyl-5-hydroxyhexyl)phthalate, the most abundant metabolite of di-(2-ethylhexyl)phthalate (DEHP), was less active than mono(2-ethylhexyl)phthalate (MEHP) as a PPAR ligand. Other derivatives oxidized at the alkyl group and benzene ring of DEHP, MEHP dibutyl phthalate and its monoester were also investigated and some affected PPAR activities. Unexpectedly, MEHP as well as its further oxidized metabolite did not show clear activity for PPAR alpha, although MEHP is believed to interact with PPAR alpha. This might imply indirect PPAR-mediated mechanisms that lead to observed biological effects such as peroxisome proliferation. (C) 2008 Elsevier Ltd. All rights reserved.

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