title: The cellular effects of a unique pesticide sulfluramid (N-ethylperfluorooctane sulphonamide) on rabbit renal proximal tubules.
abstract: The cellular effects of sulfluramid (N-ethylperfluorooctane sulphonamide, NEPFOS) and its major metabolite perfluorooctane sulphonamide (PFOS) were examined using a suspension of rabbit renal proximal tubules as a model. NEPFOS and PFOS were potent stimulators of proximal tubule basal oxygen consumption (QO(2)), with initial effects exhibited at 5-10 mum and maximal effects at 50-200 mum. The increase in basal QO(2) was ouabain insensitive, which suggests that NEPFOS and PFOS may act by uncoupling oxidative phosphorylation. Exposure of tubule suspensions to NEPFOS or PFOS concentrations of 100 mum or higher for 60 min produced tubule death, indicated by an increase in the release of lactate dehydrogenase. The tubule death did not appear to result from alkylation or lipid peroxidation, since glutathione and malondialdehyde levels were unaffected. To determine the mechanism by which NEPFOS and PFOS increased tubule QO(2), the effects of NEPFOS and PFOS on isolated renal cortical mitochondria were examined. NEPFOS (10 mum) and PFOS (5 mum) increased state-4 respiration of mitochondria in the absence of a phosphate acceptor. These results suggest that NEPFOS and PFOS uncouple oxidative phosphorylation and may produce cytotoxicity through this mechanism.
authors.affiliation: Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
authors.forename: R G
authors.initials: RG
authors.lastname: Schnellmann