期刊
ARCHIVES OF TOXICOLOGY
卷 83, 期 10, 页码 909-924出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00204-009-0450-y
关键词
Metabolomics; Perfluorooctanesulfonamides; Perfluorooctanesulfonate; Peroxisomal acyl Co-A oxidase; Superoxide dismutase
类别
资金
- University of Iowa
- National Institute of Environmental Health Sciences, NIH [ES05605, ES013661, ES012475]
- Kentucky Agricultural Experiment Statio
- NIH [P30-CA086862]
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 a parts per thousand << perfluorooctanesulfonamide similar to N-ethyl perfluorooctanesulfonamidoacetate a parts per thousand << perfluorooctanesulfonamidoethanol similar to 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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