The effects of perfluorodecanoic acid on hepatic stearoyl-coenzyme A desaturase and mixed function oxidase activities in rats.
Perfluorodecanoic acid (PFDA) causes a dioxin-like toxic syndrome and alters the hepatic oleate/stearate ratio in rats. The acute toxic effects of a single ip dose (50 mg/kg) of PFDA on hepatic stearoyl-CoA desaturase and mixed function oxidases were studied in male Fischer-344 rats, 14 days after dosing. PFDA causes a marked decrease in food intake in rats, resulting in severe body weight loss with delayed lethality (2-3 weeks after dosing). To distinguish the effects of hypophagia from those caused by PFDA, pair-fed control rats were used in addition to ad libitum-fed controls. Stearoyl-CoA desaturase activity, responsible for the conversion of stearoyl-CoA to oleoyl-CoA, was absent in both PFDA-dosed rats and their pair-fed controls at Day 14. Electron transfer through the desaturase system was significantly reduced in PFDA-treated rats only, and in these rats there was a significant reduction in microsomal cytochrome b5, an important component of this electron transfer system. Pentobarbital sleeping times were significantly prolonged in both the PFDA-dosed and pair-fed rats, as compared with the ad libitum-fed controls. This effect was more pronounced in PFDA-dosed rats. Waking plasma pentobarbital concentration was similar in all treatment groups. Hepatic microsomal cytochrome P-450 content was unaffected. Aminopyrine N-demethylase activity was greatly reduced in PFDA-dosed rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Van Rafelghem
M J
MJ
Department of Pharmacology and Toxicology, Wright State University, Dayton, Ohio 45435.
Andersen
M E
ME
D000818:Animals; D003580:Cytochromes / Q000378:metabolism; D003652:Decanoic Acids / Q000494:pharmacology*; D044943:Fatty Acid Desaturases / Q000378:metabolism*; D005466:Fluorocarbons / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D010424:Pentobarbital / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D012890:Sleep / Q000187:drug effects; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism*; D013997:Time Factors
D003580:Cytochromes; D003652:Decanoic Acids; D005466:Fluorocarbons; C036567:perfluorodecanoic acid; D006899:Mixed Function Oxygenases; D044943:Fatty Acid Desaturases; D013230:Stearoyl-CoA Desaturase; D010424:Pentobarbital