Peroxisome proliferator perfluorodecanoic acid alters glutathione and related enzymes.
Previously we have shown that treatment with the peroxisome proliferator perfluorodecanoic acid (PFDA) significantly increased hepatic reduced glutathione (GSH) content without altering the activity of selenium-glutathione peroxidase. In this study we examined some potential mechanisms by which PFDA treatment increases GSH levels. Male Sprague-Dawley rats were given a single injection of 0, 8.8, 17.5, and 35 mg PFDA in corn oil per kg body weight. Twelve days later the effects of PFDA on the activities of enzymes associated with GSH synthesis, utilization, and regeneration were assessed. The results showed that in a dose-dependent manner, PFDA treatment significantly decreased the activity of gamma-glutamylcysteine synthetase, while the activities of NADPH-generating enzymes, malic enzyme, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase were increased. PFDA treatment also dose dependently decreased cytosolic, but not microsomal, glutathione S-transferase activity, and the activity of glutathione reductase was decreased by the highest dose of PFDA. The data obtained suggest that increased hepatic GSH levels following PFDA treatment may result from increased regeneration and/or decreased utilization.
Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40506-0054, USA.
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Glauert
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D000818:Animals; D003652:Decanoic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005466:Fluorocarbons / Q000494:pharmacology*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000378:metabolism; D008297:Male; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D010734:Phosphogluconate Dehydrogenase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions / Q000187:drug effects* / Q000201:enzymology*
D003652:Decanoic Acids; D005466:Fluorocarbons; D020025:Peroxisome Proliferators; C036567:perfluorodecanoic acid; D008291:Malate Dehydrogenase; D010734:Phosphogluconate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D005978:Glutathione