Abstract
Perfluorooctane sulfonate (PFOS) is a perfluoroalkyl acid (PFAA) and a persistent environmental contaminant found in the tissues of humans and wildlife. Although blood levels of PFOS have begun to decline, health concerns remain because of the long half-life of PFOS in humans. Like other PFAAs, such as, perfluorooctanoic acid (PFOA), PFOS is an activator of peroxisome proliferator-activated receptor-alpha (PPARα) and exhibits hepatocarcinogenic potential in rodents. PFOS is also a developmental toxicant in rodents where, unlike PFOA, its mode of action is independent of PPARα. Wild-type (WT) and PPARα-null (Null) mice were dosed with 0, 3, or 10 mg/kg/day PFOS for 7 days. Animals were euthanized, livers weighed, and liver samples collected for histology and preparation of total RNA. Gene profiling was conducted using Affymetrix 430_2 microarrays. In WT mice, PFOS induced changes that were characteristic of PPARα transactivation including regulation of genes associated with lipid metabolism, peroxisome biogenesis, proteasome activation, and inflammation. PPARα-independent changes were indicated in both WT and Null mice by altered expression of genes related to lipid metabolism, inflammation, and xenobiotic metabolism. Such results are similar to studies done with PFOA and are consistent with modest activation of the constitutive androstane receptor (CAR), and possibly PPARγ and/or PPARβ/δ. Unique treatment-related effects were also found in Null mice including altered expression of genes associated with ribosome biogenesis, oxidative phosphorylation, and cholesterol biosynthesis. Of interest was up-regulation of Cyp7a1, a gene which is under the control of various transcription regulators. Hence, in addition to its ability to modestly activate PPARα, PFOS induces a variety of PPARα-independent effects as well.
Highlights
Perfluoroalkyl acids (PFAAs) are stable man-made perfluorinated organic molecules that have been utilized since the 1950s in the manufacture of a variety of industrial and commercial products such as fire fighting foams, fluoropolymers for the automobile and aerospace industry, paper food packaging, stain-resistant coatings for carpet and fabric, cosmetics, insecticides, lubricants, and nonstick coatings for cookware
perfluorooctane sulfonate (PFOS) induced hepatomegaly and altered the expression of genes related to a number of biological functions known to be regulated by PPARα including lipid metabolism, peroxisome biogenesis, proteasome activation, and the inflammatory response [41,42,43,44,45]
These data are in agreement with previous studies done in either the adult or fetal rodent [46,47,48,49,50]. Among those effects found to be independent of PPARα was altered expression of genes associated with xenobiotic metabolism, including up-regulation of the constitutive androstane receptor (CAR) inducible gene, Cyp2b10
Summary
Perfluoroalkyl acids (PFAAs) are stable man-made perfluorinated organic molecules that have been utilized since the 1950s in the manufacture of a variety of industrial and commercial products such as fire fighting foams, fluoropolymers for the automobile and aerospace industry, paper food packaging, stain-resistant coatings for carpet and fabric, cosmetics, insecticides, lubricants, and nonstick coatings for cookware. One such PFAA, perfluorooctane sulfonate (PFOS), was identified nearly a decade ago as a persistent organic pollutant which could be found in the tissues of wildlife throughout the globe [2].
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.