Gestational and lactational exposure to potassium perfluorooctanesulfonate (K+PFOS) in rats: Toxicokinetics, thyroid hormone status, and related gene expression

Chang, Shu Ching; Ehresman, David J.; Bjork, James A.; Wallace, Kendall B.; Parker, George A.; Stump, Donald G.; Butenhoff, John L.

doi:10.1016/j.reprotox.2009.01.005

Cited by 106 publications

(49 citation statements)

References 66 publications

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“…Expression of Heme oxygenase 1 (Ho-1), Multidrug resistance-associated protein (Mrp) 2, Mrp4, UDP-glucuronosyltransferase (Ugt) 1a6, and Superoxide dismutase (Sod) 1, which are highly associated with Nrf2 signaling (Thimmulappa et al, 2002; Dreger et al, 2009), were increased in the current study (37.6%, 26.0%, 334%, 65.2%, and 48.1% higher than vehicle-treated group). PFOS decreased Cytochrome P450, family 7, subfamily A, polypeptide 1 (Cyp7a1) by 78.5%, which is consistent with the previous study (Chang et al ., 2009). …”

Section: Resultssupporting

confidence: 93%

PFOS induces adipogenesis and glucose uptake in association with activation of Nrf2 signaling pathway

Shimpi

Armstrong

et al. 2016

Toxicology and Applied Pharmacology

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PFOS is a chemical of nearly ubiquitous exposure in humans. Recent studies have associated PFOS exposure to adipose tissue-related effects. The present study was to determine whether PFOS alters the process of adipogenesis and regulates insulin-stimulated glucose uptake in mouse and human preadipocytes. In murine-derived 3T3-L1 preadipocytes, PFOS enhanced hormone-induced differentiation to adipocytes and adipogenic gene expression, increased insulin-stimulated glucose uptake at concentrations ranging from 10 to 100 µM, and enhanced Glucose transporter type 4 and Insulin receptor substrate-1 expression. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), NAD(P)H dehydrogenase, quinone 1 and Glutamate-cysteine ligase, catalytic subunit were significantly induced in 3T3-L1 cells treated with PFOS, along with a robust induction of Antioxidant Response Element (ARE) reporter in mouse embryonic fibroblasts isolated from ARE-hPAP transgenic mice by PFOS treatment. Chromatin immunoprecipitation assays further illustrated that PFOS increased Nrf2 binding to ARE sites in mouse Nqo1 promoter, suggesting that PFOS activated Nrf2 signaling in murine-derived preadipocytes. Additionally, PFOS administration in mice (100 µg/kg/day) induced adipogenic gene expression and activated Nrf2 signaling in epididymal white adipose tissue. Moreover, the treatment on human visceral preadipocytes illustrated that PFOS (5 and 50 µM) promoted adipogenesis and increased cellular lipid accumulation. It was observed that PFOS increased Nrf2 binding to ARE sites in association with Nrf2 signaling activation, induction of Peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α expression, and increased adipogenesis. This study points to a potential role PFOS in dysregulation of adipose tissue expandability, and warrants further investigations on the adverse effects of persistent pollutants on human health.

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Section: Resultssupporting

confidence: 93%

PFOS induces adipogenesis and glucose uptake in association with activation of Nrf2 signaling pathway

Shimpi

Armstrong

et al. 2016

Toxicology and Applied Pharmacology

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“…Likewise, Kemp's ridley and loggerhead sea turtles are at risk of thyroid disruption, and all sea turtle species, even herbivorous greens, at average PFOS exposure are at risk of a Fetal serum PFOS concentration was determined by Lau et al [25] using a different set of female rats that were exposed to the same dose and duration as in Bjork et al [24]. b Male pup serum PFOS concentration was determined in Chang et al [30] at PND21, similar to the timing of the LOAEL at PND17. c This is not the internal serum concentration, but rather the embryos' water exposure concentration.…”

Section: Resultsmentioning

confidence: 99%

Perfluoroalkyl contaminants in plasma of five sea turtle species: Comparisons in concentration and potential health risks

Keller

Ngai

McNeill

et al. 2012

Enviro Toxic and Chemistry

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Abstract-The authors compared blood plasma concentrations of 13 perfluoroalkyl contaminants (PFCs) in five sea turtle species with differing trophic levels. Wild sea turtles were blood sampled from the southeastern region of the United States, and plasma was analyzed using liquid chromatography tandem mass spectrometry. Mean concentrations of perfluorooctane sulfonate (PFOS), the predominant PFC, increased with trophic level from herbivorous greens (2.41 ng/g), jellyfish-eating leatherbacks (3.95 ng/g), omnivorous loggerheads (6.47 ng/g), to crab-eating Kemp's ridleys (15.7 ng/g). However, spongivorous hawksbills had surprisingly high concentrations of PFOS (11.9 ng/g) and other PFCs based on their trophic level. These baseline concentrations of biomagnifying PFCs demonstrate interesting species and geographical differences. The measured PFOS concentrations were compared with concentrations known to cause toxic effects in laboratory animals, and estimated margins of safety (EMOS) were calculated. Small EMOS (<100), suggestive of potential risk of adverse health effects, were observed for all five sea turtle species for immunosuppression. Estimated margins of safety less than 100 were also observed for liver, thyroid, and neurobehavorial effects for the more highly exposed species. These baseline concentrations and the preliminary EMOS exercise provide a better understanding of the potential health risks of PFCs for conservation managers to protect these threatened and endangered species.

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“…PFBS is a recent introduction to the market and is less persistent than other PFASs. For example, the t 1/2 of PFBS is 3.1 h in male rats [21] and it is far shorter compared to PFOA (6-8 days).…”

Section: Discussionmentioning

confidence: 98%

The inhibition of human and rat 11β-hydroxysteroid dehydrogenase 2 by perfluoroalkylated substances

Zhao

Lian²,

Chu

et al. 2011

The Journal of Steroid Biochemistry and Molecular Biology

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Gestational and lactational exposure to potassium perfluorooctanesulfonate (K+PFOS) in rats: Toxicokinetics, thyroid hormone status, and related gene expression

Cited by 106 publications

References 66 publications

PFOS induces adipogenesis and glucose uptake in association with activation of Nrf2 signaling pathway

PFOS induces adipogenesis and glucose uptake in association with activation of Nrf2 signaling pathway

Perfluoroalkyl contaminants in plasma of five sea turtle species: Comparisons in concentration and potential health risks

The inhibition of human and rat 11β-hydroxysteroid dehydrogenase 2 by perfluoroalkylated substances

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