Effect of perfluorooctane sulfonate (PFOS) on influenza A virus-induced mortality in female B6C3F1 mice

Article (PDF Available)inThe Journal of Toxicological Sciences 34(6):687-91 · December 2009with25 Reads
Impact Factor: 1.29 · DOI: 10.2131/jts.34.687 · Source: PubMed
Abstract
Recent studies showed that perfluorooctane sulfonate (PFOS) affects the mammalian immune system at levels reportedly found in the general human population. It has been demonstrated that exposure to immunotoxic chemicals may diminish the host resistance of animals to various pathogenic challenges and enhance mortality. Therefore, the current study was carried out to characterize the effect of a 21 day pre-administration of zero, 5, or 25 microg PFOS/kg bw/day in female B6C3F1 mice on host resistance to influenza A virus infection. At the end of PFOS exposure, body/organ weights did not significantly change whereas PFOS distribution in blood plasma, spleen, thymus and lung was dose-dependently increased. PFOS exposure in mice resulted a significant increase in emaciation and mortality in response to influenza A virus. The effective plasma concentrations in female mice were at least several fold lower than reported mean blood PFOS levels from occupationally exposed humans, and fell in the upper range of blood concentrations of PFOS in the normal human population and in a wide range of wild animals. Hence, it should be important to clarify the precise mechanism(s) for excess mortality observed in the high dose group.

Full-text (PDF)

Available from: Dr. Keerthi S. Guruge, Feb 17, 2015
INTRODUCTION
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Page 5
    • "These studies found detectable levels of PFAAs, with serum concentrations approaching toxic levels in sea turtles (Keller et al., 2005Keller et al., , 2012). Additional laboratory studies have shown PFAAs to possess toxic biological effects in developmental (Lau et al., 2003), immune (Peden-Adams et al., 2008; DeWitt et al., 2009; Guruge et al., 2009), and neurological systems (Zhang et al., 2011). Crocodilians are an important PFAA sentinel species, due to the fact they are apex predators (hold the potential of accumulating high levels of PFAAs), exhibit high site fidelity, and have inherently long lifespans (70e100 years) in aquatic environments vulnerable to anthropogenic runoff. "
    [Show abstract] [Hide abstract] ABSTRACT: Perfluorinated alkyl acids (PFAAs) are environmental contaminants that have been used in many products for over 50 years. Interest and concern has grown since 2000 on the widespread presence of PFAAs, when it was discovered that PFAAs were present in wildlife samples around the northern hemisphere. Since then, several studies have reported PFAAs in wildlife from many locations, including the remote regions of Antarctica and the Arctic. Although there are a multitude of studies, few have reported PFAA concentrations in reptiles and wildlife in the Southern Hemisphere. This study investigated the presence of PFAAs in the plasma of Nile crocodiles (Crocodylus niloticus) from South Africa. Crocodiles were captured from five sites in and around the Kruger National Park, South Africa, and plasma samples examined for PFAAs. Perfluorooctane sulfonate (PFOS) was the most frequent PFAA detected; with median values of 13.5 ng/g wet mass in crocodiles. In addition to PFOS, long chain perfluorinated carboxylic acids were also detected. Correlations between total length and PFAA load were investigated, as were differences in PFAA accumulation between sexes. No correlations were seen between crocodile size, nor were there sex-related differences. Spatial differences were examined and significant differences were observed in samples collected from the different sites (p < 0.05). Flag Boshielo Dam had the highest PFOS measurements, with a median concentration of 50.3 ng/g wet mass, when compared to the other sites (median concentrations at other sites below 14.0 ng/g wet mass). This suggests a point source of PFOS in this area.
    Full-text · Article · Jul 2016
    • "PFAAs are harmful to animals: neurotoxicity of perfluorooctane sulfonate (PFOS) in rats and mice after a single oral exposure (Sato et al., 2009) and after a sub chronic exposure (Kawamoto et al., 2011 ) is suggested to be underlined by its similar effect on membrane potential and increased intracellular Ca ++ shown in paramecium (Kawamoto et al., 2008 ). PFOS increased influenza A virus -induced mortality likely by affecting the mammalian immune system (Guruge et al., 2009), and reduced superoxide dismutase activity and total anti-oxidation capacity in neonatal mice (Liu et al., 2009 ). "
    [Show abstract] [Hide abstract] ABSTRACT: Perfluoroalkyl acids (PFAAs) have been widely used since 1950s. The long chained-PFAAs, such as perfluorooctanoic acid (PFOA) are persistent and bio-accumulative, and are detected in humans. PFOA, which is a peroxisome proliferator activated receptor (PPAR) α agonist, has been suggested to be a carcinogen in epidemiological and animal studies. In some studies PFOA is shown to be non-mutagenic in Ames and micronucleus tests, but in other studies it caused oxidative DNA damage and micronucleus formation. However, there has been no report that has examined whether PFOA-induced genotoxicity is mediated by PPARα. In order to relate genotoxicity of PFAAs to PPARα, we conducted two kinds of comet assays (cellular and acellular), a micronucleus (MN) test, and a TK mutation assay with and without PPARαantagonists by using human lymphoblastoid cells. PFAAs at 125-1000 µg/mL showed positive responses in the cellular comet assay but not in the MN test and TK mutation assay. A PPARα antagonist GW6471 (2 µg/mL) only partly reduced PFOA-induced DNA damage (in the cellular comet assay), but abolished PFOA-induced intracellular ROS formation. PFAAs with 8-12 carbons also showed positive responses in the acellular comet assay where there is no cellular function such as PPAR. Therefore, PFOA-induced DNA damage was partly related to the oxidative stress via PPARα, without manifestation of chromosome aberration and point mutation in this cell line.
    Article · Jan 2016
    • "Future studies should investigate the gene expression profiles of the thymus because T cells originate from the bone marrow and mature in the thymus, which are then released to the peripheral tissues. In addition, the thymus has been shown to accumulate PFOS at a similar magnitude as that observed in the mouse spleen [17]. In addition, the effects of PFOS on the thymus have been previously reported [16]. "
    [Show abstract] [Hide abstract] ABSTRACT: Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that is used worldwide and is continuously being detected in biota and the environment, thus presenting potential threats to the ecosystem and human health. Although PFOS is highly immunotoxic, its underlying molecular mechanisms remain largely unknown. The present study examined PFOS-induced immunotoxicity in the mouse spleen and explored its underlying mechanisms by gene expression profiling. Oral exposure of male BALB/c mice for three weeks followed by one-week recovery showed that a 10 mg/kg/day PFOS exposure damaged the splenic architecture, inhibited T-cell proliferation in response to mitogen, and increased the percentages of T helper (CD3(+)CD4(+)) and cytotoxic T (CD3(+)CD8(+)) cells, despite the decrease in the absolute number of these cells. A delayed type of PFOS immunotoxicity was observed, which mainly occurred during the recovery period. Global gene expression profiling of mouse spleens and QRT-PCR analyses suggest that PFOS inhibited the expression of genes involved in cell cycle regulation and NRF2-mediated oxidative stress response, and upregulated those in TCR signaling, calcium signaling, and p38/MAPK signaling pathways. Western blot analysis confirmed that the expressions of CAMK4, THEMIS, and CD3G, which were involved in the upregulated pathways, were induced upon PFOS exposure. Acute PFOS exposure modulated calcium homoeostasis in splenocytes. These results indicate that PFOS exposure can activate TCR signaling and calcium ion influx, which provides a clue for the potential mechanism of PFOS immunotoxicity. The altered signaling pathways by PFOS treatment as revealed in the present study might facilitate in better understanding PFOS immunotoxicity and explain the association between immune disease and PFOS exposure. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Full-text · Article · Aug 2015
    Qi-Yan Lv Qi-Yan LvBin Wan Bin WanLiang-Hong Guo Liang-Hong Guo+1more author...[...]
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