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

Journal Article · · PPAR Research
DOI:https://doi.org/10.1155/2007/15481· OSTI ID:1626197
 [1];  [2];  [3];  [2];  [2];  [2];  [4];  [5]
  1. University of Kentucky, Lexington, KY (United States); University of Iowa, Iowa City, IA (United States); DOE/OSTI
  2. University of Kentucky, Lexington, KY (United States)
  3. University of Kentucky, Lexington, KY (United States); Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
  4. GSF-National Research Center For Environment and Health, Institute of Toxicology, Neuherberg (Germany)
  5. Tranzyme Pharma Inc., Sherbrooke, QC (Canada)
+ Show Author Affiliations
The purpose of this study was to determine the effects of PCBs and PBBs on peroxisome proliferator-activated receptor- α -(PPAR α -) associated enzyme activities or protein levels. Male Sprague-Dawley rats were administered a single IP injection (150 μ mol/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 PPAR α , these agents are therefore exerting their carcinogenic and promoting activities by some other mechanism.
Research Organization:
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
Sponsoring Organization:
Alexander von Humboldt Foundation; Kentucky Agricultural Experiment Station; National Institutes of Health (NIH); Peace Fellowship from the Egyptian Embassy; USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC05-00OR22725
OSTI ID:
1626197
Journal Information:
PPAR Research, Journal Name: PPAR Research Vol. 2007; ISSN 1687-4757
Publisher:
HindawiCopyright Statement
Country of Publication:
United States
Language:
English

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