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Perfluorooctanoic acid exposure triggers oxidative stress in the mouse pancreas.

ABSTRACT: Perfluorooctanoic acid (PFOA) is used in the manufacture of many industrial and commercial products. PFOA does not readily decompose in the environment, and is biologically persistent. Human epidemiologic and animal studies suggest that PFOA exposure elicits adverse effects on the pancreas. While multiple animal studies have examined PFOA-mediated toxicity in the liver, little is known about the potential adverse effects of PFOA on the pancreas. To address this, we treated C57Bl/6 mice with vehicle, or PFOA at doses of 0.5, 2.5 or 5.0 mg/kg BW/day for 7 days. Significant accumulation of PFOA was found in the serum, liver and pancreas of PFOA-treated animals. Histopathologic examination of the pancreas revealed focal ductal hyperplasia in mice treated with 2.5 and 5.0 mg/kg BW/day PFOA, while inflammation was observed only in the high dose group. Elevated serum levels of amylase and lipase were observed in the 2.5 mg/kg BW/day PFOA treatment group. In addition, PFOA exposure resulted in a dose-dependent increase in the level of the lipid peroxidation product 8-iso-PGF_2? and induction of the antioxidant response genes Sod1, Sod2, Gpx2 and Nqo1. Our findings provide additional evidence that the pancreas is a target organ for PFOA-mediated toxicity and suggest that oxidative stress may be a mechanism through which PFOA induces histopathological changes in the pancreas.

SUBMITTER: Kamendulis LM

PROVIDER: S-EPMC5598264 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Perfluorooctanoic acid exposure triggers oxidative stress in the mouse pancreas.

Kamendulis Lisa M LM Wu Qiangen Q Sandusky George E GE Hocevar Barbara A BA

Toxicology reports 20140802

Perfluorooctanoic acid (PFOA) is used in the manufacture of many industrial and commercial products. PFOA does not readily decompose in the environment, and is biologically persistent. Human epidemiologic and animal studies suggest that PFOA exposure elicits adverse effects on the pancreas. While multiple animal studies have examined PFOA-mediated toxicity in the liver, little is known about the potential adverse effects of PFOA on the pancreas. To address this, we treated C57Bl/6 mice with vehi ...[more]

PMID: 28962265

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Project description:To investigate the particle size distribution of particulate matter and the concentration of specific perfluorinated compounds in indoor dust samples from several locations. Then, we used cell-based assays to investigate the effect of perfluorinated compounds on human corneal epithelial (HCEpiC), endothelial cells (HCEC) and retinal pigment epithelial cells (RPE). Indoor dust samples were collected at five different locations and PM50-10, PM10-2.5, and PM2.5-1 were fractionized. The presence and levels of 8:2 fluorotelomer alcohol, 10:2 fluorotelomer alcohol, and perfluorooctanoic acid were detected by gas chromatography-mass spectrometry. The effect of perfluorooctanoic acid on the activation of reactive oxygen species, transepithelial resistance as well as the expression of interleukin (IL)-6 and IL-8 were determined. The basolateral media of human corneal epithelial or human corneal endothelial cells were used to treat human corneal endothelial or retinal pigment epithelial cells, respectively to indicate the potential of ocular surface inflammation may result in retinal inflammation. Among perfluorinated compounds, only perfluorooctanoic acid was detected in all indoor dust samples. Perfluorooctanoic acid had the highest concentration among all perfluorinated compounds in the samples. Exposure to perfluorooctanoic acid impaired tight junction sealing and increased the levels of reactive oxygen species in human corneal epithelial cells. In human corneal epithelial cells, secretion of IL-6 and IL-8 in both apical and basolateral media was promoted significantly by perfluorooctanoic acid treatment. Stimulation with the basolateral media from perfluorooctanoic acid-treated human corneal epithelial cells induced inflammation in human corneal endothelial cells. The treatment of retinal pigment epithelial cells with the basolateral media from stimulated human corneal endothelial cells also elicited the secretion of proinflammatory cytokines. The results indicate that perfluorooctanoic acid exposure impaired the tight junction of corneal cells and caused inflammatory reactions in the retina. Exposure of the cornea to perfluorooctanoic acid contained in particulate matter might induce oxidative stress and inflammation in the retina and represent a risk factor for age-related macular degeneration.

Project description:BackgroundPerfluorooctanoic acid (PFOA) has been linked to cancer in occupational mortality studies and animal toxicologic research.ObjectiveWe investigated the relationship between PFOA exposure and cancer among residents living near the DuPont Teflon-manufacturing plant in Parkersburg, West Virginia (WV).MethodsOur analyses included incident cases of 18 cancers diagnosed from 1996 through 2005 in five Ohio (OH) counties and eight WV counties. For analyses of each cancer outcome, controls comprised all other cancers in the study data set except kidney, pancreatic, testicular, and liver cancers, which have been associated with PFOA in animal or human studies. We applied logistic regression models to individual-level data to calculate adjusted odds ratios (AORs) and confidence intervals (CIs). For the combined analysis of OH and WV data, the exposure of interest was resident water district. Within OH, geocoded addresses were integrated with a PFOA exposure model to examine the relationship between cancer odds and categories of estimated PFOA serum.ResultsOur final data set included 7,869 OH cases and 17,238 WV cases. There was a positive association between kidney cancer and the very high and high serum exposure categories [AOR = 2.0 (95% CI: 1.0, 3.9) n = 9 and 2.0 (95% CI: 1.3, 3.2) n = 22, respectively] and a null association with the other exposure categories compared with the unexposed. The largest AOR was for testicular cancer with the very high exposure category [2.8 (95% CI: 0.8, 9.2) n = 6], but there was an inverse association with the lower exposure groups, and all estimates were imprecise because of small case numbers.ConclusionsOur results suggest that higher PFOA serum levels may be associated with testicular, kidney, prostate, and ovarian cancers and non-Hodgkin lymphoma. Strengths of this study include near-complete case ascertainment for state residents and well-characterized contrasts in predicted PFOA serum levels from six contaminated water supplies.

Project description:BackgroundPerfluorooctanoic acid (PFOA or C8) has hepatotoxic effects in animals. Cross-sectional epidemiologic studies suggest PFOA is associated with liver injury biomarkers.ObjectivesWe estimated associations between modeled historical PFOA exposures and liver injury biomarkers and medically validated liver disease.MethodsParticipants completed surveys during 2008-2011 reporting demographic, medical, and residential history information. Self-reported liver disease, including hepatitis, fatty liver, enlarged liver and cirrhosis, was validated with healthcare providers. Alanine aminotransferase (ALT), ?-glutamyltransferase (GGT) and direct bilirubin, markers of liver toxicity, were obtained from blood samples collected in the C8 Health Project (2005-2006). Historically modeled PFOA exposure, estimated using environmental fate and transport models and participant residential histories, was analyzed in relation to liver biomarkers (n = 30,723, including 1,892 workers) and liver disease (n = 32,254, including 3,713 workers).ResultsModeled cumulative serum PFOA was positively associated with ALT levels (p for trend < 0.0001), indicating possible liver toxicity. An increase from the first to the fifth quintile of cumulative PFOA exposure was associated with a 6% increase in ALT levels (95% CI: 4, 8%) and a 16% increased odds of having above-normal ALT (95% CI: odds ratio: 1.02, 1.33%). There was no indication of association with either elevated direct bilirubin or GGT; however, PFOA was associated with decreased direct bilirubin. We observed no evidence of an effect of cumulative exposure (with or without a 10-year lag) on all liver disease (n = 647 cases), nor on enlarged liver, fatty liver, and cirrhosis only (n = 427 cases).ConclusionResults are consistent with previous cross-sectional studies showing association between PFOA and ALT, a marker of hepatocellular damage. We did not observe evidence that PFOA increases the risk of clinically diagnosed liver disease.CitationDarrow LA, Groth AC, Winquist A, Shin HM, Bartell SM, Steenland K. 2016. Modeled perfluorooctanoic acid (PFOA) exposure and liver function in a Mid-Ohio Valley community. Environ Health Perspect 124:1227-1233;?http://dx.doi.org/10.1289/ehp.1510391.

Dataset Information

Perfluorooctanoic acid exposure triggers oxidative stress in the mouse pancreas.

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Perfluorooctanoic acid exposure triggers oxidative stress in the mouse pancreas.

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