Effects of perfluoro-n-decanoic acid on the respiratory activity of isolated rat liver mitochondria.
The toxic responses of rats to a single dose of perfluorodecanoic acid (PFDA) include reduced food consumption, severe body weight loss ("wasting syndrome"), and hypothermia. Recent studies have suggested that some of these effects may be due to alterations of basic metabolic processes in animals treated with PFDA. In order to test this hypothesis the effects of PFDA on respiratory activity of isolated rat liver mitochondria were examined. PFDA concentrations up to 87.5 micrograms/ml produced a linear increase in oxygen consumption during state 4 (nonphosphorylating) respiration. This suggested uncoupling of electron transport and oxidative phosphorylation was supported by the observation that PFDA released mitochondrial state 3 respiration from inhibition by oligomycin and stimulated latent ATPase activity. Concentrations of PFDA greater than 87.5 micrograms/ml produced progressively less increase in state 4 oxygen consumption, and a single high concentrations (150 micrograms/ml) completely inhibited state 3 respiration and prevented the uncoupling effect of 2,4-dinitrophenol. These observations suggest that in addition to uncoupling electron transport and oxidative phosphorylation PFDA may affect other energy-transducing functions of liver mitochondria such as inhibiting electron transport. These effects on mitochondrial respiration may help to explain the "wasting syndrome" characteristic of PFDA toxicity.
Langley
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Department of Pharmacology and Toxicology, Wright State University, School of Medicine, Dayton, Ohio.
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D003652:Decanoic Acids / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005466:Fluorocarbons / Q000633:toxicity*; D066298:In Vitro Techniques; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D003652:Decanoic Acids; D005466:Fluorocarbons; C036567:perfluorodecanoic acid