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Induction of peroxisome proliferator-activated receptor alpha (PPARα)-related enzymes by di(2-ethylhexyl) phthalate (DEHP) treatment in mice and rats, but not marmosets

  • Molecular Toxicology
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Abstract

To clarify species differences in the induction of peroxisome proliferator-activated receptor alpha (PPARα)-related enzymes by di(2-ethylhexyl)phthalate (DEHP) exposure, we investigated the inductions of PPARα and its target genes (mitochondrial medium-chain acyl-CoA dehydrogenase (MCAD) and peroxisomal keto-acyl-CoA thiolase (PT) in liver from mice (CD-1), rats (Sprague–Dawley), and marmosets (Callithrix jacchus) exposed to DEHP. Male mice and rats were treated with 0, 1.25 and 2.5 mmol/kg DEHP for 2 weeks, and marmosets with 0, 0.25, 1.25 and 6.25 mmol/kg DEHP for 15 months by gavage. Hepatic mono(2-ethylhexyl)phthalate (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 PPARα-mRNA in all animals. The treatment-induced PT expression detected either by anti-PT antibody or PT-mRNA 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 PPARα-related 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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Acknowledgments

This study was supported by a research grant from the Japan Ministry of Environment (2002), a Grant-in-Aid for Scientific Research (14370121), and a Grant-in-Aid for JSPS fellows (142531) from the Japan Society for the Promotion of Science.

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Authors and Affiliations

  1. Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Yuki Ito, Michihiro Kamijima & Tamie Nakajima

  2. Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, 1200 Matsumoto-cho, Kasugai, 487-8501, Japan

    Osamu Yamanoshita

  3. Department of Safety Science Research, Mitsubishi Research Institute Co. Ltd., Kashima, 314-0255, Japan

    Yoshimasa Kurata

  4. Department of Metabolic Regulation, Institute of Aging and Adaptation, Shinshu University Graduate School of Medicine, Matsumoto, 390-8621, Japan

    Toshifumi Aoyama

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  1. Yuki Ito
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  2. Osamu Yamanoshita
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  3. Yoshimasa Kurata
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  4. Michihiro Kamijima
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  5. Toshifumi Aoyama
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  6. Tamie Nakajima
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Correspondence to Tamie Nakajima.

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Ito, Y., Yamanoshita, O., Kurata, Y. et al. Induction of peroxisome proliferator-activated receptor alpha (PPARα)-related enzymes by di(2-ethylhexyl) phthalate (DEHP) treatment in mice and rats, but not marmosets. Arch Toxicol 81, 219–226 (2007). https://doi.org/10.1007/s00204-006-0141-x

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  • DOI: https://doi.org/10.1007/s00204-006-0141-x

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