| Perfluorooctane sulfonamides are one group of a variety of perfluorinated compounds that have been used as surfactants worldwide for more than a half of a century. Perfluorinated compounds were manufactured for their chemical and thermal inertness, and special surface-active characteristics. The remarkable versatility of these compounds in applications as surfactants on fabrics, fire retardants, anti-corrosion agents, anti-static agents for film production, oil and water resistant coatings on paper, and as insecticides made them a tremendous industrial and commercial success. This group of chemicals is characterized by carbon chains with a variety of lengths to which fluorine atoms are covalently bonded. The global distribution and environmental persistence of these compounds has generated considerable interest regarding potential toxic effects. There have been a number of studies with a variety of exposure regimens in which a wasting syndrome, or cachexia, has been observed in animals exposed to perfluorinated acids. The most prominent acute and sub-chronic high dose effects of perfluorinated acids in adult rodents and monkeys are altered lipid metabolism, hepatocellular hypertrophy and vacuolation, decreased serum cholesterol, decreased serum triglycerides, hepatomegaly, decreased body weight, and death.; The objective of the work presented here was to establish a thorough understanding of the mechanism involved in permeability transition mediated disruption of mitochondrial bioenergetics by the N-acetyl perfluorooctane sulfonamides. The model used in this work was isolated rat liver mitochondria from Sprague-Dawley rats. The primary approach to meeting this objective required an understanding of the following: (1) which of the selected group of perfluorooctanes induce the MPT; (2) characterize the sequential relationship between induction of the MPT, the release of cytochrome c, inhibition of mitochondrial respiration, and the generation of reactive oxygen species (ROS) (Is the MPT the result of ROS or the initiator of ROS production?); (3) identify the specific functional group or groups responsible for MPT induction by the N-acetyl perfluorooctane sulfonamides; (4) determine with which, if any, specific mitochondrial membrane proteins do the N-acetyl perfluorooctane sulfonamides interact; and (5) characterize the effect on mitochondrial function as a result of any identified interaction between N-acetyl perfluorooctane sulfonamides and mitochondrial membrane proteins. |
