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Title of Journal: Arch Toxicol

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Abbravation: Archives of Toxicology

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Springer-Verlag

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1432-0738

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Induction of peroxisome proliferatoractivated rec

Authors: Yuki Ito Osamu Yamanoshita Yoshimasa Kurata Michihiro Kamijima Toshifumi Aoyama Tamie Nakajima
Publish Date: 2006/08/26
Volume: 81, Issue: 3, Pages: 219-226
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Abstract

To clarify species differences in the induction of peroxisome proliferatoractivated receptor alpha PPARαrelated enzymes by di2ethylhexylphthalate DEHP exposure we investigated the inductions of PPARα and its target genes mitochondrial mediumchain acylCoA dehydrogenase MCAD and peroxisomal ketoacylCoA thiolase PT in liver from mice CD1 rats Sprague–Dawley and marmosets Callithrix jacchus exposed to DEHP Male mice and rats were treated with 0 125 and 25 mmol/kg DEHP for 2 weeks and marmosets with 0 025 125 and 625 mmol/kg DEHP for 15 months by gavage Hepatic mono2ethylhexylphthalate MEHP levels were significantly higher in mice and rats than in marmosets The constitutive expression of hepatic PPARα was 5–7 times greater in rats and mice than in marmosets but DEHP treatment did not induce PPARαmRNA in all animals The treatmentinduced PT expression detected either by antiPT antibody or PTmRNA levels in the liver only from mice and rats and the induction of the mRNA was greater in the latter than in the former Thus DEHP used in this experiment influenced the peroxisomal enzymes in mice and rats but did not affect the mitochondrial enzymes in any animals or the peroxisomal enzymes in marmosets These results suggest that there are species differences in the induction of PPARαrelated enzymes especially in peroxisomal enzymes by DEHP treatment and their underlying mechanism may in part reside in the different constitutive levels of PPARα and different forming levels of MEHP


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