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PPAR Research
Volume 2007, Article ID 15481, 5 pages
http://dx.doi.org/10.1155/2007/15481
Research Article

Suppression of Peroxisomal Enzyme Activities and Cytochrome P450 4A Isozyme Expression by Congeneric Polybrominated and Polychlorinated Biphenyls

1Graduate Center for Toxicology, University of Kentucky, Funkhouser Building, Lexington, KY 40506-0054, USA
2Department of Occupational and Environmental Health, College of Public Health, University of Iowa, 124 IREH 100 Oakdale Campus, Iowa City, IA 52242-5000, USA
3Oak Ridge National Laboratory, Oak Ridge, TN 37830, USA
4Graduate Center for Nutritional Sciences, University of Kentucky, Funkhouser Building, Lexington, KY 40506-0054, USA
5GSF-National Research Center For Environment and Health, Institute of Toxicology, Ingolstädter Landstraße 1, Neuherberg 85716, Germany
6Tranzyme Pharma Inc., 3001 12th Avenue North, Building Z5-3037, Sherbrooke, QC J1H 5N4, Canada

Received 30 May 2007; Accepted 10 August 2007

Academic Editor: Jihan Youssef

Copyright © 2007 Larry W. Robertson et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The purpose of this study was to determine the effects of PCBs and PBBs on peroxisome proliferator-activated receptor-α-(PPARα-) associated enzyme activities or protein levels. Male Sprague-Dawley rats were administered a single IP injection (150 μmol/kg) of either 3,3′,4,4′-tetrabromobiphenyl, 3,3′,4,4′-tetrachlorobiphenyl, 3,3′,5,5′-tetrabromobiphenyl, 2′,3,3′,4,5-pentachlorobiphenyl, 3,3′,4,4′,5-pentachlorobiphenyl, 2,2′,3,3′,5,5′-hexachlorobiphenyl, or 3,3′,4,4′,5,5′-hexabromobiphenyl in corn oil (10 ml/kg). One week later, the activities of catalase, peroxisomal fatty acyl-CoA oxidase, and peroxisomal beta-oxidation as well as cytochrome P450 4A (CYP4A) protein content were determined in subcellular liver fractions. None of the peroxisomal enzyme activities were significantly increased by any of the halogenated biphenyl congeners tested. Except for minor (approx. 25%) increases in the total CYP4A content following treatment with 2,2′,3,3′,5,5′-hexachlorobiphenyl and 3,3′,5,5′-tetrabromobiphenyl, CYP4A protein contents were not increased by any treatment. The two Ah receptor agonists, 3,3′,4,4′-tetrabromobiphenyl and 3,3′,4,4′,5-pentachlorobiphenyl, significantly diminished the liver content of CYP4A proteins and activities of the peroxisomal enzymes studied. Since a range of congeners with different biologic and toxicologic activities were selected for this study, it may be concluded that the polyhalogenated biphenyls do not induce peroxisome proliferation in the male rat, but rather certain members of this class of compounds down regulate peroxisome-associated enzymes. Since PCBs and PBBs do not increase enzyme activities and expression of proteins associated with PPARα, these agents are therefore exerting their carcinogenic and promoting activities by some other mechanism.