The effects of perfluorodecanoic acid on hepatic stearoyl-coenzyme A desaturase and mixed function oxidase activities in rats

Abstract

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, pairfed 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 b 5, 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. Although pair-fed controls also had reduced demethylase activity, it was not as pronounced as in PFDA-dosed rats, and was probably due to the fasted condition of these animals. Although the mechanism of action of PFDA is not known, it is possible that PFDA affects microsomal enzymes by altering the structure and/or function of the membranes in which they are located, through effects on lipid metabolism.