Associations of perfluorinated chemical serum concentrations and biomarkers of liver function and uric acid in the US population (NHANES), 2007–2010

Gleason, Jessie A.; Post, Gloria B.; Fagliano, Jerald

doi:10.1016/j.envres.2014.10.004

Cited by 151 publications

(108 citation statements)

References 35 publications

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“…In the NHANES study, PCB exposures were associated with ‘unexplained alanine aminotransferase (ALT) elevation’, a surrogate marker for fatty liver [561]. The observed association between PCB exposures and ALT was subsequently confirmed in NHANES by two other independent groups using different statistical techniques; and also in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort [562-564]. Likewise, associations between organochlorine pesticides or their metabolites and liver enzymes have been seen for ALT [562] and gamma glutamyl transferase [565].…”

Section: Mdcs and Metabolism-relevant Diseasesmentioning

confidence: 99%

Metabolism disrupting chemicals and metabolic disorders

Heindel

Blumberg

Cave

et al. 2017

Reproductive Toxicology

814

651

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The recent epidemics of metabolic diseases, obesity, type 2 diabetes(T2D), liver lipid disorders and metabolic syndrome have largely been attributed to genetic background and changes in diet, exercise and aging. However, there is now considerable evidence that other environmental factors may contribute to the rapid increase in the incidence of these metabolic diseases. This review will examine changes to the incidence of obesity, T2D and non-alcoholic fatty liver disease (NAFLD), the contribution of genetics to these disorders and describe the role of the endocrine system in these metabolic disorders. It will then specifically focus on the role of endocrine disrupting chemicals (EDCs) in the etiology of obesity, T2D and NAFLD while finally integrating the information on EDCs on multiple metabolic disorders that could lead to metabolic syndrome. We will specifically examine evidence linking EDC exposures during critical periods of development with metabolic diseases that manifest later in life and across generations.

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Section: Mdcs and Metabolism-relevant Diseasesmentioning

confidence: 99%

Metabolism disrupting chemicals and metabolic disorders

Heindel

Blumberg

Cave

et al. 2017

Reproductive Toxicology

814

651

View full text Add to dashboard Cite

show abstract

“…A literature review was conducted to determine concentrations of PFOA and PFOS in human serum of United States residents (Chang et al, 2014, Emmett et al, 2006, Gleason et al, 2015, Landsteiner et al, 2014, Lau, 2012, Olsen et al, 2007). Populations were categorized into three different groups based on the potential for exposure to either compound.…”

Section: Figurementioning

confidence: 99%

“…A recent study revealed that more than 98% of human serum samples examined in the United States contain detectable levels of PFOA/PFOS, which were dose dependently associated with positive liver function tests (Gleason et al, 2015). The general population of the United States has both PFOA and PFOS present in their blood at concentrations ranging from approximately 10–100 nM (Chang et al, 2014, Gleason et al, 2015, Lau, 2012) (Figure 1). As expected, residents of the areas surrounding cities including Decatur, Alabama and Cottage Grove, Minnesota, where the 3M company manufactured PFOA and PFOS, had higher concentrations in their blood, as a consequence of watershed contamination.…”

Section: Introductionmentioning

confidence: 99%

The role of hepatocyte nuclear factor 4-alpha in perfluorooctanoic acid- and perfluorooctanesulfonic acid-induced hepatocellular dysfunction

Beggs

McGreal

McCarthy

et al. 2016

Toxicology and Applied Pharmacology

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Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), chemicals present in a multitude of consumer products, are persistent organic pollutants. Both compounds induce hepatotoxic effects in rodents, including steatosis, hepatomegaly and liver cancer. The mechanisms of PFOA- and PFOS-induced hepatic dysfunction are not completely understood. We present evidence that PFOA and PFOS induce their hepatic effects via targeting hepatocyte nuclear factor 4-alpha (HNF4α). Human hepatocytes treated with PFOA and PFOS at a concentration relevant to occupational exposure caused a decrease in HNF4α protein without affecting HNF4α mRNA or causing cell death. RNA sequencing analysis combined with Ingenuity Pathway Analysis of global gene expression changes in human hepatocytes treated with PFOA or PFOS indicated alterations in the expression of genes involved in lipid metabolism and tumorigenesis, several of which are regulated by HNF4α. Further investigation of specific HNF4α target gene expression revealed that PFOA and PFOS could promote cellular dedifferentiation and increase cell proliferation by down regulating positive targets (differentiation genes such as CYP7A1) and inducing negative targets of HNF4α (pro-mitogenic genes such as CCND1). Furthermore, in silico docking simulations indicated that PFOA and PFOS could directly interact with HNF4α in a similar manner to endogenous fatty acids. Collectively, these results highlight HNF4α degradation as novel mechanism of PFOA and PFOS-mediated steatosis and tumorigenesis in human livers.

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“…PFOA has been detected in worldwide human populations. Data from NHANES 1999-2000, 2003-2004, 2005-2008-2010 showed that the geometric mean PFOA concentrations in serum were 5.2, 3.95, 3.92, 4.13 and 3.06 ng/mL in the U.S. population, respectively [6,7]. In occupational exposure population, the median serum PFOA level could reach 775 ng/mL [8].…”

Section: Introductionmentioning

confidence: 99%

Involvement of NRF2 in Perfluorooctanoic Acid-Induced Testicular Damage in Male Mice1

Liu¹,

Yang²,

Wu³

et al. 2015

Biology of Reproduction

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Perfluorooctane acid (PFOA) is a hazardous environmental pollutant that has been reported to exert adverse effects on animal and human health. In this study, male mice were orally administered different concentrations of PFOA (2.5, 5, or 10 mg/kg/day) to evaluate the reproductive toxicity. Exposure to PFOA for 14 consecutive days obviously disrupted seminiferous tubules and reduced sperm count. The highest concentration of PFOA (10 mg/kg/day) caused growth retardation and diminished absolute testis weight. Furthermore, PFOA treatment significantly increased the generation of oxidative stress indicators malondialdehyde and hydrogen peroxide, decreased the expression of transcription factor NRF2, and inhibited the activities of antioxidant enzymes superoxide dismutase and catalase in the testis. Moreover, PFOA exposure up-regulated p-p53 and BAX expression and down-regulated BCL-2 expression in the testis. These results indicated that PFOA-induced male reproductive disorders might be involved in developmental impairment and inhibition of NRF2-mediated antioxidant response in the testis of mice.

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Associations of perfluorinated chemical serum concentrations and biomarkers of liver function and uric acid in the US population (NHANES), 2007–2010

Cited by 151 publications

References 35 publications

Metabolism disrupting chemicals and metabolic disorders

Metabolism disrupting chemicals and metabolic disorders

The role of hepatocyte nuclear factor 4-alpha in perfluorooctanoic acid- and perfluorooctanesulfonic acid-induced hepatocellular dysfunction

Involvement of NRF2 in Perfluorooctanoic Acid-Induced Testicular Damage in Male Mice1

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