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Subacute exposure to N-ethyl perfluorooctanesulfonamidoethanol results in the formation of perfluorooctanesulfonate and alters superoxide dismutase activity in female rats |
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| Authors: | Wei Xie Qian Wu Izabela Kania-Korwel Job C. Tharappel Sanjay Telu Mitchell C. Coleman Howard P. Glauert Kurunthachalam Kannan S. V. S. Mariappan Douglas R. Spitz Jamie Weydert Hans-Joachim Lehmler |
| Affiliation: | 1. Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, 100 Oakdale Campus, #221 IREH, Iowa City, IA, 52242, USA 2. Wadsworth Center, New York State Department of Health and Department of Environmental Health Sciences, State University of New York, Empire State Plaza, Albany, NY, 12201-0509, USA 3. Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY, 40506, USA 4. Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA, 52242, USA 5. Graduate Center for Toxicology, University of Kentucky, Lexington, KY, 40506, USA 6. Department of Chemistry, College of Liberal Arts and Sciences, The University of Iowa, Iowa City, IA, 52242, USA 7. Department of Pathology, Carver College of Medicine, The University of Iowa, Iowa City, IA, 52242, USA |
| Abstract: | Perfluorooctanesulfonamides, such as N-ethyl perfluorooctanesulfonamidoethanol (N-EtFOSE), are large scale industrial chemicals but their disposition and toxicity are poorly understood despite significant human exposure. The hypothesis that subacute exposure to N-EtFOSE, a weak peroxisome proliferator, causes a redox imbalance in vivo was tested using the known peroxisome proliferator, ciprofibrate, as a positive control. Female Sprague–Dawley rats were treated orally with N-EtFOSE, ciprofibrate or corn oil (vehicle) for 21 days, and levels of N-EtFOSE and its metabolites as well as markers of peroxisome proliferation and oxidative stress were assessed in serum, liver and/or uterus. The N-EtFOSE metabolite profile in liver and serum was in good agreement with reported in vitro biotransformation pathways in rats and the metabolite levels decreasing in the order perfluorooctanesulfonate ? perfluorooctanesulfonamide ~ N-ethyl perfluorooctanesulfonamidoacetate ? perfluorooctanesulfonamidoethanol ~ N-EtFOSE. Although N-EtFOSE treatment significantly decreased the growth rate, increased relative liver weight and activity of superoxide dismutases (SOD) in liver and uterus (total SOD, CuZnSOD and MnSOD), a metabolic study revealed no differences in the metabolome in serum from N-EtFOSE-treated and control animals. Ciprofibrate treatment increased liver weight and peroxisomal acyl Co-A oxidase activity in the liver and altered antioxidant enzyme activities in the uterus and liver. According to NMR metabolomic studies, ciprofibrate treated animals had altered serum lipid profiles compared to N-EtFOSE-treated and control animals, whereas putative markers of peroxisome proliferation in serum were not affected. Overall, this study demonstrates the biotransformation of N-EtFOSE to PFOS in rats that is accompanied by N-EtFOSE-induced alterations in antioxidant enzyme activity. |
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