Dose-related effects of perfluorodecanoic acid on growth, feed intake and hepatic peroxisomal beta-oxidation.
The effects of the persistent peroxisome proliferator, perfluorodecanoic acid (PFDA), on growth, feed intake and the enzyme activities associated with peroxisomal beta-oxidation were studied in female Sprague Dawley rats. Rats received one of six levels of PFDA (0, 0.3, 1.0, 3.0, 10.0 or 30.0 mg/kg/injection) in four IP doses at 2-week intervals. Rats with cumulative doses of less than or equal to 12.0 mg/kg did not differ from control rats in growth or feed intake, while rats receiving cumulative doses of greater than or equal to mg/kg lost weight and decreased their feed intake. Rats which received cumulative doses between these levels increased their feed intake but did not significantly alter their body weight. Total peroxisomal beta-oxidation was decreased in a dose-related manner, whereas the liver to body weight ratio and the activities of individual enzymes comprising the peroxisomal beta-oxidation system, namely fatty acyl-CoA oxidase, enoyl-CoA hydratase, 3-hydroxy-acyl-CoA dehydrogenase, and thiolase, were increased. This study clearly shows that the inhibition of peroxisomal beta-oxidation by PFDA is not reflected in the in vitro measurement of the individual enzyme activities comprising this pathway.
Borges
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Graduate Center for Toxicology, University of Kentucky, Lexington 40506-0054.
Robertson
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LW
Peterson
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Glauert
H P
HP
D000818:Animals; D003652:Decanoic Acids / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D005260:Female; D005466:Fluorocarbons / Q000633:toxicity*; D006128:Growth / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008830:Microbodies / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D015430:Weight Gain / Q000187:drug effects
D003652:Decanoic Acids; D005466:Fluorocarbons; C036567:perfluorodecanoic acid