Dose-related effects of perfluorodecanoic acid on growth, feed intake and hepatic peroxisomal β-oxidation

The effects of the persistent peroxisome proliferator, perfluorodecanoic acid (PFDA), on growth, feed intake and the enzyme activities associated with peroxisomal β-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 ≤ 12.0 mg/kg did not differ from control rats in growth or feed intake, while rats receiving cumulative doses of ≥40 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 β-oxidation was decreased in a dose-related manner, whereas the liver to body weight ratio and the activities of individual enzymes comprising the peroxisomal β-oxidation system, namely fatty acyl-CoA oxidase, enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and thiolase, were increased. This study clearly shows that the inhibition of peroxisomal ß-oxidation by PFDA is not reflected in the in vitro measurement of the individual enzyme activities comprising this pathway.

[1]  R. Hill,et al.  Bovine liver crotonase (enoyl coenzyme A hydratase). EC 4.2.1.17 L-3-hydroxyacyl-CoA hydrolyase. , 1975, Methods in enzymology.

[2]  Melvin E. Andersen,et al.  Perfluoro-n-decanoic acid: Induction of peroxisomal β-oxidation by a fatty acid with dioxin-like toxicity , 1988, Lipids.

[3]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[4]  B. Middleton.  3-Ketoacyl-CoA thiolases of mammalian tissues. , 1975, Methods in enzymology.

[5]  J. V. Vanden Heuvel,et al.  Disposition of perfluorodecanoic acid in male and female rats. , 1991, Toxicology and applied pharmacology.

[6]  T. Hashimoto,et al.  Peroxisomal beta oxidation system of rat liver. Copurification of enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase. , 1979, Biochemical and biophysical research communications.

[7]  C. J. McGrath,et al.  Effect of exchange rate return on volatility spill-over across trading regions , 2012 .

[8]  W. Jones,et al.  The effect of peroxisome proliferators on microsomal, peroxisomal, and mitochondrial enzyme activities in the liver and kidney. , 1987, Drug metabolism reviews.

[9]  G. W. Snedecor.  Statistical Methods , 1964 .

[10]  R. Peterson,et al.  Synthesis of 14C‐labeled perfluorooctanoic and perfluorodecanoic acids; purification of perfluorodecanoic acid , 1987 .

[11]  J. Warren,et al.  HEPATIC AND RENAL EFFECTS OF PEROXISOME PROLIFERATORS: BIOLOGICAL IMPLICATIONS * , 1982, Annals of the New York Academy of Sciences.

[12]  James G. Speight,et al.  Surface-active materials from Athabasca oil sands , 1980 .

[13]  Report of the American Institute of Nurtition ad hoc Committee on Standards for Nutritional Studies. , 1977, The Journal of nutrition.

[14]  E. Lock,et al.  Biochemical mechanisms of induction of hepatic peroxisome proliferation. , 1989, Annual review of pharmacology and toxicology.

[15]  N. Lalwani,et al.  Induction, immunochemical identity and immunofluorescence localization of an 80 000-molecular-weight peroxisome-proliferation-associated polypeptide (polypeptide PPA-80) and peroxisomal enoyl-CoA hydratase of mouse liver and renal cortex. , 1981, The Biochemical journal.

[16]  J. Reddy,et al.  Carcinogenesis by hepatic peroxisome proliferators: evaluation of the risk of hypolipidemic drugs and industrial plasticizers to humans. , 1983, Critical reviews in toxicology.

[17]  D. L. Cinti,et al.  Dual action of 2-decynoyl coenzyme A: inhibitor of hepatic mitochondrial trans-2-enoyl coenzyme A reductase and peroxisomal bifunctional protein and substrate for the mitochondrial beta-oxidation system. , 1988, Archives of biochemistry and biophysics.

[18]  M E Andersen,et al.  The acute toxicity of perfluorooctanoic and perfluorodecanoic acids in male rats and effects on tissue fatty acids. , 1983, Toxicology and applied pharmacology.

[19]  M E Andersen,et al.  Toxic effects of nonadecafluoro-n-decanoic acid in rats. , 1986, Toxicology and applied pharmacology.

[20]  W. Anderson,et al.  Preparation of protein synthesis initiation factors IF-M1, IF-M2A, and IF-M2B from rabbit reticulocytes. , 1974, Methods in enzymology.

[21]  P. Lazarow.  Assay of peroxisomal beta-oxidation of fatty acids. , 1981, Methods in enzymology.

[22]  J. G. Bieri.  Potassium requirement of the growing rat. , 1977, The Journal of nutrition.

[23]  R. Hill,et al.  [18] Bovine liver crotonase (enoyl coenzyme A hydratase) , 1975 .

[24]  R. A. Guenthner,et al.  Surface Active Materials from Perfluorocarboxylic and Perfluorosulfonic Acids , 1962 .

[25]  Y. Kawashima,et al.  Sex-related difference in the inductions by perfluoro-octanoic acid of peroxisomal beta-oxidation, microsomal 1-acylglycerophosphocholine acyltransferase and cytosolic long-chain acyl-CoA hydrolase in rat liver. , 1989, The Biochemical journal.

[26]  Richard E. Peterson,et al.  Perfluorodecanoic acid and lipid metabolism in the rat , 1988, Lipids.

[27]  M Tanaka,et al.  The induction of peroxisome proliferation in rat liver by perfluorinated fatty acids, metabolically inert derivatives of fatty acids. , 1985, Journal of biochemistry.

[28]  Larry W. Robertson,et al.  Effect of the peroxisome proliferator perfluorodecanoic acid on growth and lipid metabolism in Sprague Dawley rats fed three dietary levels of selenium , 2005, Archives of Toxicology.

[29]  R. Peterson,et al.  Interrelationships between energy and fat metabolism and hypophagia in rats treated with perfluorodecanoic acid. , 1988, Toxicology letters.

[30]  M Ylinen,et al.  Tissue distribution and elimination of perfluorodecanoic acid in the rat after single intraperitoneal administration. , 1990, Pharmacology & toxicology.

[31]  Reddy Jk,et al.  Carcinogenesis by Hepatic Peroxisome Proliferators: Evaluation of the Risk of Hypolipidemic Drugs and Industrial Plasticizers to Humans , 1983 .

[32]  J. G. Bieri.  Second Report of the ad hoc Committee on Standards for Nutritional Studies , 1980 .

[33]  Russell K Yamazaki,et al.  Determination of peroxisomal fatty acyl-CoA oxidase activity using a lauroyl-CoA-based fluorometric assay. , 1986, Biochimica et biophysica acta.