Perfluorooctane Sulfonate Treatment Research Articles

Antioxidative-related genes expression following perfluorooctane sulfonate (PFOS) exposure in the intertidal mud crab, Macrophthalmus japonicus

Perfluorooctane sulfonate (PFOS) is a persistent environmental contaminant that is used as a surfactant in various industries and consumer products. The intertidal mud crab, Macrophthalmus japonicus, is one of the most abundant macrobenthic creatures. In this study, we have investigated the effect of PFOS on the molecular transcription of antioxidant and detoxification signaling in M. japonicus crab. The selected stress response genes were superoxide dismutases (CuZnSOD and MnSOD), catalase (CAT), glutathione peroxidase (GPx), phospholipid hydroperoxide glutathione peroxidase (PHGPx), peroxiredoxin (Prx), and thioredoxin reductase (TrxR). Significant up-regulation of SODs and CAT was observed after 24 and 96 h exposure to PFOS at different concentrations. The gene expression levels of GPx, PHGPx, and TrXR were significantly up-regulated after exposure to PFOS for 96 h. The transcript levels of CAT and PHGPx were induced in dose- and time-dependent manners after PFOS treatments. However, Prx gene expression was significantly up-regulated in M. japonicus crabs exposed to 10 and 30 μg L-1 PFOS for 96 h. Additionally, PFOS toxicity in M. japonicus induced reduced survival rates at relatively high concentrations of PFOS exposure. Our findings support the contention that exposures to PFOS induced the response of genes related to oxidative stress and detoxification in M. japonicus crabs.

Potential toxicity of environmentally relevant perfluorooctane sulfonate (PFOS) concentrations to yellow-legged gull Larus michahellis embryos

Perfluooctane sulfonate (PFOS) is considered an emerging pollutant because of its wide distribution in both aquatic and terrestrial ecosystems, as well as its potential toxicity to living organisms. Although PFOS environmental levels and the adverse effects on classical model organisms in toxicological studies are well known, including developmental alterations and alteration of oxidative status, its toxicity to free-living species has been seldom investigated. The aim of this study was to assess the potential toxicity of environmental levels of PFOS to yellow-legged gull (Larus michahellis) embryos under field experimental conditions. In a within-clutch experimental design, we injected two PFOS concentrations (100ng PFOS/g egg weight and 200ng PFOS/g egg weight) in ovo soon after laying. Eggs were collected when they reached the cracking stage. We investigated the effects of PFOS treatment, laying order and sex on both morphological and biochemical endpoints of embryos. Specifically, we assessed changes in embryo body mass and tarsus length, as well as in liver and brain mass. Moreover, the imbalance of oxidative status was evaluated in both liver and brain from embryos by measuring total antioxidant capacity (TAC) and total oxidant status (TOS), while the levels of protein carbonyl content (PCO) and DNA fragmentation were measured as oxidative and genetic damage endpoints, respectively. The concentrations of PFOS we tested did not significantly alter the morphological endpoints, independently of laying order and sex. Similarly, embryo oxidative status and oxidative and genetic damage were not significantly affected by PFOS in ovo exposure. These findings suggest that current environmental PFOS levels do not affect early development of yellow-legged gull embryos.

In vivo immunotoxicity of perfluorooctane sulfonate in BALB/c mice: Identification of T-cell receptor and calcium-mediated signaling pathway disruption through gene expression profiling of the spleen

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.

Reactive oxygen species mediate nitric oxide production through ERK/JNK MAPK signaling in HAPI microglia after PFOS exposure

Perfluorooctane sulfonate (PFOS), an emerging persistent contaminant that is commonly encountered during daily life, has been shown to exert toxic effects on the central nervous system (CNS). However, the molecular mechanisms underlying the neurotoxicity of PFOS remain largely unknown. It has been widely acknowledged that the inflammatory mediators released by hyper-activated microglia play vital roles in the pathogenesis of various neurological diseases. In the present study, we examined the impact of PFOS exposure on microglial activation and the release of proinflammatory mediators, including nitric oxide (NO) and reactive oxidative species (ROS). We found that PFOS exposure led to concentration-dependent NO and ROS production by rat HAPI microglia. We also discovered that there was rapid activation of the ERK/JNK MAPK signaling pathway in the HAPI microglia following PFOS treatment. Moreover, the PFOS-induced iNOS expression and NO production were attenuated after the inhibition of ERK or JNK MAPK by their corresponding inhibitors, PD98059 and SP600125. Interestingly, NAC, a ROS inhibitor, blocked iNOS expression, NO production, and activation of ERK and JNK MAPKs, which suggested that PFOS-mediated microglial NO production occurs via a ROS/ERK/JNK MAPK signaling pathway. Finally, by exposing SH-SY5Y cells to PFOS-treated microglia-conditioned medium, we demonstrated that NO was responsible for PFOS-mediated neuronal apoptosis.

Perfluorooctane sulfonate mediates microglial activation and secretion of TNF-α through Ca²⁺-dependent PKC-NF-кB signaling.

Perfluorooctane sulfonate (PFOS), a ubiquitous pollutant widely found in the environment and biota, can cause numerous adverse effects on human health. In recent years, PFOS's toxic effects on the central nervous system (CNS) have been shown. However, we still have a lot to study in the underlying molecular mechanism of PFOS's neurotoxicity. Microglia, the innate immune cells of CNS, are critically implicated in various neurological diseases caused by pro-inflammatory mediators. In our research, we found that HAPI microglia secreted tumor necrosis factor-alpha (TNF-α) after PFOS exposure in time-dependent and dose-dependent way. We also discovered that intracellular concentration of free Ca(2+) ([Ca(2+)]i) significantly increased after PFOS treatments. It was noteworthy here the secretion of TNF-α mediated by PFOS was blocked by Ca(2+) inhibitor and protein kinase C (PKC) inhibitor. Besides these, we had learned as well that PFOS brought about the up-regulation of phosphorylated nuclear factor kappa B (NF-кB) p65 expression and accelerated degradation of NF-κB inhibitor alpha (IкBα), however, these effects could be attenuated or blocked by Ca(2+) inhibitor and PKC inhibitor. Finally, through treating SH-SY5Y cells with PFOS-treated microglial conditioned medium, we demonstrated that TNF-α mediated neuronal apoptosis. To sum up, our research had shown, for the first time, that the distinct TNF-α secretion brought by PFOS in HAPI microglia, was achieved through the Ca(2+)-dependent PKC-NF-кB signaling, subsequently participating in neuronal loss.

Connexin 43 mediates PFOS-induced apoptosis in astrocytes

Perfluorooctane sulfonate (PFOS) is a man-made environmental pollutant that is toxic to mammals. However, the neurotoxic effects of PFOS remain largely unexplored. In this study, we determined the role of an astrocyte specific gap junction protein, connexin 43 (Cx43), in PFOS-induced apoptosis. The rate of astrocyte apoptosis was higher in cortex astrocytes after PFOS treatment. These astrocytes also showed up-regulated expression of Cx43 and higher levels of cleaved caspase-3. Elevated ROS accumulation and decreased ΔΨm also confirmed the presence of PFOS-induced apoptosis. However, the exposure of astrocytes to PFOS together with carbenoxolone (CBX) significantly reduced both Cx43 and cleaved caspase-3 levels. These results indicate that Cx43 plays a proapoptotic role in PFOS-induced apoptosis in cortex astrocyte cells.

PFOS Disturbs BDNF-ERK-CREB Signalling in Association with Increased MicroRNA-22 in SH-SY5Y Cells.

Perfluorooctane sulfonate (PFOS), a ubiquitous environmental pollutant, is neurotoxic to mammalian species. However, the underlying mechanism of its neurotoxicity was unclear. We hypothesized that PFOS suppresses BDNF expression to produce its neurotoxic effects by inhibiting the ERK-CREB pathway. SH-SY5Y human neuroblastoma cells were exposed to various concentrations of PFOS to examine the role of the BDNF-ERK-CREB signalling pathway in PFOS-induced apoptosis and cytotoxicity. Furthermore, to ascertain the mechanism by which PFOS reduces BDNF signalling, we examined the expression levels of miR-16 and miR-22, which potentially regulate BDNF mRNA translation at the posttranscriptional level. Results indicated that PFOS significantly decreased cell viability and induced apoptosis in SH-SY5Y cells. In addition, BDNF and pERK protein levels decreased after PFOS treatment; however, pCREB protein levels were significantly elevated in PFOS treated groups. TrkB protein expression increased in the 10 μM and 50 μM PFOS groups and significantly decreased in the 100 μM PFOS group. Our results demonstrated that PFOS exposure decreased miR-16 expression and increased miR-22 expression, which may represent a possible mechanism by which PFOS decreases BDNF protein levels. PFOS may inhibit BDNF-ERK-CREB signalling by increasing miR-22 levels, which may, in part, explain the mechanism of PFOS neurotoxicity.

The use of spontaneous behavior, swimming performances and metabolic rate to evaluate toxicity of PFOS on topmouth gudgeon Pseudorasbora parva

Perfluorooctane sulfonate (PFOS) is a ubiquitous environmental contaminant that has been found to pose various risks to fish health and the safety of aquatic ecosystem. Swimming performance is an integrated index of fitness in fish. However, little research has sought on the effects of PFOS on swimming performances of fish. Experiments were carried out to clarify the impacts of acute exposure to PFOS on behavior, swimming ability and metabolic rate in topmouth gudgeon (Pseudorasbora parva), to understand the underlying ecotoxicological effects of waterborne PFOS exposure on fish physiology and behavior. Fish were exposed to PFOS (0, 0.5, 2, 8 or 32 mg/L) for 96 h. Afterwards, the routine metabolic rate (RMR), spontaneous swimming behavior (SSB), fast-start swimming performance (FSP) and critical swimming speed (Ucrit) of the topmouth gudgeon were examined. The results show reduced behavioral performance and increased physiological stress with increasing PFOS concentration. Both RMR, SSB and Ucrit were significantly affected by PFOS exposure (p < 0.05). The lowest observed effect concentration (LOEC) is 2 mg/L for SSB. PFOS treatment resulted in increased RMR (p = 0.001) and decreased Ucrit (p = 0.005), whereas FSP was not influenced by PFOS (p > 0.05). The results indicate that the anaerobic swimming capacity was conserved, but the metabolic level, SSB and aerobic swimming performance in topmouth gudgeon were susceptible to PFOS contamination, and hence might be useful as considerable potential biomarkers of pollution.

Perfluorooctane sulfonate blocked autophagy flux and induced lysosome membrane permeabilization in HepG2 cells

Perfluorooctane sulfonate (PFOS) is an emerging persistent organic pollutant widely distributed in the environment, wildlife and human. In this study, as observed under the transmission electron microscope, PFOS increased autophagosome numbers in HepG2 cells, and it was confirmed by elevated LC3-II levels in Western blot analysis. PFOS increased P62 level and chloroquine failed to further increase the expression of LC3-II after PFOS treatment, indicating that the accumulation of autophagosome was due to impaired degradation rather than increased formation. With acridine orange staining, we found PFOS caused lysosomal membrane permeabilization (LMP). In this study, autophasome formation inhibitor 3-methyladenine protected cells against PFOS toxicity, autophagy stimulator rapamycin further decreased cell viability and increased LDH release, cathepsin inhibitor did not influence cell viability of PFOS-treated HepG2 cells significantly. These further supported the notion that autophagic cell death contributed to PFOS-induced hepatotoxicity. In summary, the data of the present study revealed that PFOS induced LMP and consequent blockage of autophagy flux, leading to an excessive accumulation of the autophagosomes and turning autophagy into a destructive process eventually. This finding will provide clues for effective prevention and treatment of PFOS-induced hepatic disease.

Biodegradation of perfluorooctanesulfonate (PFOS) as an emerging contaminant

Perfluorooctanesulfonate (PFOS) is a compound of global concern because of its persistence and bioaccumulation in the environment. Nevertheless, little is known of the potential for PFOS biodegradation, even though the importance of characterizing the function and activity of microbial populations detected in the environment has been discussed. This study focused on the biodegradation of PFOS by a specific microorganism. Through this study, we have identified the aerobic microorganism for the specific decomposition of PFOS from wastewater treatment sludge, as a well-known sink for environmental PFOS. This species was Pseudomonas aeruginosa strain HJ4 with a 99% similarity, a mesophilic rod type bacteria (30–37°C). A pH range of 7–9 was determined to be optimal for the growth of strain HJ4. In this study approximately 67% over a range of concentrations (1400–1800μgL−1) for PFOS was biologically decomposed by P. aeruginosa after 48h incubation. This result is reported here for the first time, which strongly pertains to the efficient biodegradation of PFOS. Therefore, our study is considered a major advancement in sustainable PFOS treatment.

Regulation of corticosterone secretion is modified by PFOS exposure at different levels of the hypothalamic–pituitary–adrenal axis in adult male rats

Perfluorooctane sulfonate (PFOS) is a fluorinated compound and a Persistent Organic Pollutant which can disrupt the endocrine system. This work was undertaken to evaluate the possible effects of PFOS exposure on the regulation of corticosterone secretion in adrenal and pituitary glands and at hypothalamic level in adult male rat, and to evaluate the possible morphological alterations induced by PFOS in this endocrine tissue. Adult male rats were orally treated with 0.5, 1.0, 3.0 and 6.0mg of PFOS/kg/day for 28 days. Corticosterone, adrenocorticotropic hormone (ACTH) and corticotrophin-releasing hormone (CRH) secretion decreased in PFOS-treated rats. After PFOS exposure, relative expression of adrenocorticotropic hormone receptor (ACTHr) and proopiomelanocortin (POMC) genes was increased in adrenal and in pituitary glands, respectively; while relative expression of ACTHr and CRH genes decreased in hypothalamus with the doses of 0.5 and 1.0mg/kg/day. PFOS treatment increased relative nitric oxide synthase 1 and 2 (NOS1 and NOS2) gene expression in the adrenal gland, and incremented superoxide dismutase activity. PFOS exposure induces a global inhibition of the hypothalamic–pituitary–adrenal (HPA) axis activity, and small morphological changes were observed in adrenal zona fasciculata cells.

Perfluorooctane Sulfonate Disturbs Nanog Expression through miR-490-3p in Mouse Embryonic Stem Cells

Perfluorooctane sulfonate (PFOS) poses potential risks to reproduction and development. Mouse embryonic stem cells (mESCs) are ideal models for developmental toxicity testing of environmental contaminants in vitro. However, the mechanism by which PFOS affects early embryonic development is still unclear. In this study, mESCs were exposed to PFOS for 24 h, and then general cytotoxicity and pluripotency were evaluated. MTT assay showed that neither PFOS (0.2 µM, 2 µM, 20 µM, and 200 µM) nor control medium (0.1% DMSO) treatments affected cell viability. Furthermore, there were no significant differences in cell cycle and apoptosis between the PFOS treatment and control groups. However, we found that the mRNA and protein levels of pluripotency markers (Sox2, Nanog) in mESCs were significantly decreased following exposure to PFOS for 24 h, while there were no significant changes in the mRNA and protein levels of Oct4. Accordingly, the expression levels of miR-145 and miR-490-3p, which can regulate Sox2 and Nanog expressions were significantly increased. Chrm2, the host gene of miR-490-3p, was positively associated with miR-490-3p expression after PFOS exposure. Dual luciferase reporter assay suggests that miR-490-3p directly targets Nanog. These results suggest that PFOS can disturb the expression of pluripotency factors in mESCs, while miR-145 and miR-490-3p play key roles in modulating this effect.

Mineralization Behavior of Fluorine in Perfluorooctanesulfonate (PFOS) during Thermal Treatment of Lime-Conditioned Sludge

The fate and transport of the fluorine in perfluorooctanesulfonate (PFOS) during the thermal treatment of lime-conditioned sludge were observed using both qualitative and quantitative X-ray diffraction techniques. Two main fluorine mineralization mechanisms leading to the substantial formation of CaF2 and Ca5(PO4)3F phases were observed. They had a close relationship with the thermal treatment condition and the PFOS content of the sludge. At low temperatures (300-600 °C), CaF2 dominated in the product and increases in treatment time and temperature generally enhanced the fluorine transformation. However, at higher temperatures (700-900 °C), increases in treatment time and temperature had a negative effect on the overall efficiency of the fluorine crystallization. The results suggest that in the high temperature environment there were greater losses of gaseous products such as HF and SiF4 in the transformation of CaF2 to Ca5(PO4)3F, the hydrolysis of CaF2, and the reaction with SiO2. The quantitative analysis also showed that when treating sludge with low PFOS content at high temperatures, the formation of Ca5(PO4)3F may be the primary mechanism for the mineralization of the fluorine in PFOS. The overall results clearly indicate the variations in the fate and transport of fluorine in PFOS when the sludge is subject to different PFOS contents and treatment types, such as heat drying or incineration.

Perfluorooctane sulfonate (PFOS) affects hormone receptor activity, steroidogenesis, and expression of endocrine‐related genes in vitro and in vivo

Perfluorooctane sulfonate (PFOS) is a widespread and persistent chemical in the environment. We investigated the endocrine-disrupting effects of PFOS using a combination of in vitro and in vivo assays. Reporter gene assays were used to detect receptor-mediated (anti-)estrogenic, (anti-)androgenic, and (anti-)thyroid hormone activities. The effect of PFOS on steroidogenesis was assessed both at hormone levels in the supernatant and at expression levels of hormone-induced genes in the H295R cell. A zebrafish-based short-term screening method was developed to detect the effect of PFOS on endocrine function in vivo. The results indicate that PFOS can act as an estrogen receptor agonist and thyroid hormone receptor antagonist. Exposure to PFOS decreased supernatant testosterone (T), increased estradiol (E2) concentrations in H295R cell medium and altered the expression of several genes involved in steroidogenesis. In addition, PFOS increased early thyroid development gene (hhex and pax8) expression in a concentration-dependent manner, decreased steroidogenic enzyme gene (CYP17, CYP19a, CYP19b) expression, and changed the expression pattern of estrogen receptor production genes (esr1, esr2b) after 500 µg/L PFOS treatment in zebrafish embryos. These results indicate that PFOS has the ability to act as an endocrine disruptor both in vitro and in vivo by disrupting the function of nuclear hormone receptors, interfering with steroidogenesis, and altering the expression of endocrine-related genes in zebrafish embryo.

Induction of p53-mediated apoptosis in splenocytes and thymocytes of C57BL/6 mice exposed to perfluorooctane sulfonate (PFOS)

Perfluorooctane sulfonate (PFOS) is a persistent environmental contaminant found in human and wildlife tissues. It has been reported that PFOS can cause atrophy of the immune organs and apoptosis of immunocytes in rodents. However, the mechanism behind such cause is still unclear. To understand the model of cell death and its mechanism on lymphoid cells in vivo, we conducted a dose/response experiment in which 4 groups of male adult C57BL/6 mice (12 mice per group) were dosed daily by oral gavage with PFOS at 0, 0.0167, 0.0833, or 0.8333mg/kg/day, yielding targeted Total Administered Dose (TAD) of 0, 1, 5, or 50mg PFOS/kg, respectively, over 60days. The results showed that spleen and thymus weight were significantly reduced in the highest PFOS-dose-group (TAD 50mg PFOS/kg) compared to the control group, whereas liver weight was significantly increased. We analyzed the cell death via apoptosis with an annexin-V/propidium iodide assay by flow cytometry, and observed that both the percentage of apoptosis and the expression of the pro-apoptotic proteins p53 in splenocytes and thymocytes increased in a dose-related manner after PFOS treatment. We also observed that PFOS induced p53-dependent apoptosis through the cooperation between the Bcl-xl down regulation without changing the Bcl-2 and Bax expression. The down regulation of Bcl-xl was strongly indicating mitochondrial involvement in apoptosis. It is confirmed by the release of cytochrome c and activation of caspase-3. All of these findings establish an important role of p53 and mitochondrial function in PFOS induced toxic environment in the host.

Transcription of genes involved in fat metabolism in chicken embryos exposed to the peroxisome proliferator-activated receptor alpha (PPARα) agonist GW7647 or to perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA)

Perfluoroalkyl acids (PFAAs) such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are developmental toxicants in various animal classes, including birds. Both compounds interact with peroxisome proliferator-activated receptors (PPARs), but it is not known whether activation of PPARs is involved in their embryo toxicity in birds. We exposed chicken embryos via egg injection at a late developmental stage to GW7647, a potent PPARα agonist in mammals, and to PFOS or PFOA. Mortality was induced by PFOS and PFOA but not by GW7647. Transcripts of a number of genes activated by PPARα agonists in mammals were analyzed in liver and kidney of 18-day-old embryos. Several of the genes were induced in both liver and kidney following exposure to GW7647. Treatment with PFOA resulted in induction of acyl-coenzyme A oxidase mRNA in liver, whereas none of the genes were significantly induced by PFOS treatment. No up-regulation of gene transcription was found in kidney following treatment with PFOS or PFOA. Principal component analysis showed that PFOA caused an mRNA expression pattern in liver more similar to the pattern induced by GW7647 than PFOS did. Our findings do not support that the embryo mortality by PFOS and PFOA in chicken embryos involves PPARα activation.

Carcinogenic potency of perfluorooctane sulfonate (PFOS) on Syrian hamster embryo (SHE) cells

Perfluorooctane sulfonate (PFOS) is the degradation product of many fluoroderivatives and a widespread environmental contaminant. Its persistence, its long half-life in humans and its toxicity explain high concerns on human health side effects in future. PFOS is suspected to be a non-genotoxic carcinogen. In the present work, we assessed carcinogenic potential of PFOS by studying morphological transformation in Syrian hamster embryo (SHE) cells; cell transformation of SHE cells is an in vitro assay recommended by the Organization for Economic Cooperation and Development to detect carcinogens, genotoxic or not. Genotoxicity of PFOS and expression of PPARs genes in SHE cells were also measured. PFOS was shown to induce cell transformation (P<0.05) at non-cytotoxic concentrations (0.2 and 2μg/mL) (P≤0.01). No genotoxic effect was recorded in the range of PFOS concentrations tested (2×10(-4) to 50μg/mL) using the single-cell gel electrophoresis (comet) assay after 5 and 24h of exposure. The expression of PPARs genes was measured by qPCR within the first 24h and after 7days of PFOS treatment. Results indicated an increased expression of ppar-β/δ isoform as early as 24h. After 7days, the increase of ppar-β/δ mRNA was significant at the concentrations inducing cell transformation (0.2 and 2μg/mL), while overexpression of ppar-γ and ppar-α did not closely relate to effective concentrations. The results indicate that PFOS behave as a non-genotoxic carcinogen and impacted PPARs genes. Its cell transforming potential paralleled an increased expression of ppar-β/δ.

Effects of perfluorooctane sulfonate (PFOS) exposure on markers of inflammation in female B6C3F1 mice

Perfluorooctane sulfonate (PFOS; 1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-heptadecafluoro-1-octanesulfonic acid) has been reported to alter humoral immune functions, but inflammatory processes following PFOS exposure have not been fully characterized. Therefore, the current study, assessed TNF-α and IL-6 concentrations in serum and peritoneal lavage fluid, numbers of splenoctyes expressing intracellular TNF-α, IL-6, IL-10 or IL-1, and ex vivo TNF-α and IL-6 production by peritoneal macrophages following either in vivo or in vitro LPS exposure. Adult female B6C3F1 mice were exposed orally for 28 days to 0, 1, 3, or 300 mg PFOS/kg total administered dose [TAD] (e.g., 0, 0.0331, 0.0993 or 9.93 mg/kg/day). Body and spleen masses were significantly reduced in the highest PFOS treatment group compared to the control group, whereas liver mass was significantly increased. Serum TNF-α levels were significantly decreased following exposure to 1 mg PFOS/kg TAD as compared to controls, while serum IL-6 levels were increased. IL-6 concentrations in peritoneal lavage fluid decreased with increasing dose. PFOS treatment did not alter numbers of splenocytes expressing intracellular levels of TNF-α, IL-10 or IL-1. Numbers of splenocytes expressing intracellular levels of IL-6 were significantly decreased in the 3 mg/kg treatment as compared to controls. Overall, these data suggest that PFOS exposure can alter some inflammatory processes, which could potentially lead to misdirected inflammatory responses.

Toxic effects of perfluorooctane sulfonate (PFOS) on wheat ( Triticum aestivum L.) plant

Toxic effects of different concentrations (0.1–200 mg L −1) of perfluorooctane sulfonate (PFOS) on wheat ( Triticum aestivum L.) were investigated using the growing and developmental indexes of wheat, including length and biomass of roots and leaves, chlorophyll, soluble protein, peroxidase (POD), superoxide dismutase (SOD) in the seedlings and permeability of root cells. The results showed that PFOS had significant ( p < 0.05) effects on the growth of wheat seedlings under the experimental conditions. At the low concentration (less than 10 mg L −1), PFOS could slightly stimulate the growth of wheat seedlings and induce the synthesis of chlorophyll and soluble protein in wheat seedlings, and whereas exceeding 10 mg L −1 PFOS treatment could exert inhibition to the elongation and biomass of roots and leaves, and lead to damage to chlorophyll accumulation and soluble protein synthesis. Furthermore, the activities of SOD and POD in wheat roots and leaves were enhanced in the tested PFOS concentrations of 0.1–10 mg L −1. However, when the concentration of PFOS was raised up to 200 mg L −1, the activity of SOD and POD decreased significantly with 12.6% and 33.7% inhibition for roots compared to the control respectively, which indicated the antioxidative defensive system in wheat seedlings might be damaged by PFOS. In addition, the permeability of wheat root cells was enhanced at the tested concentration of 0.1–200 mg L −1. When the concentration was increased to 200 mg L −1, the electrolyte leakage was promoted 2.73 times higher than in the control.

Effects of perfluorooctane sulfonate on rat thyroid hormone biosynthesis and metabolism

The potential toxicity of perfluorooctane sulfonate (PFOS), an environmentally persistent organic pollutant, is of great concern. The present study examines the ability of PFOS to disturb thyroid function and the possible mechanisms involved in PFOS-induced thyroid hormone alteration. Male Sprague-Dawley rats were exposed to 1.7, 5.0, and 15.0 mg/L of PFOS in drinking water for 91 consecutive days. Serum was collected for analysis of total and free thyroxine (T4), total triiodothyronine (T3), and thyrotrophin (TSH). Thyroid and liver were removed for the measurement of endpoints closely related to thyroid hormone biosynthesis and metabolism following PFOS exposure. Determined endpoints were the messenger RNA (mRNA) levels for two isoforms of uridine diphosphoglucuronosyl transferases (UGT1A6 and UGT1A1) and type 1 deiodinase (DIO1) in liver, sodium iodide symporter (NIS), TSH receptor (TSHR), and DIO1 in thyroid as well as the activity of thyroid peroxidase (TPO). Serum total T4 level decreased significantly at all applied dosages, whereas total T3 level increased markedly only at 1.7 mg/L of PFOS. No statistically significant toxic effects of PFOS on serum TSH were observed. Hepatic UGTIA1, but not UGT1A6, mRNA was up-regulated at 5.0 and 15.0 mg/L of PFOS. Treatment with PFOS lowered hepatic DIO1 mRNA at 15.0 mg/L but increased thyroidal DIO1 mRNA dose dependently. The activity of TPO, NIS, and TSHR mRNA in thyroid were unaffected by PFOS treatment. These results indicate that increased hepatic T4 glucuronidation via UGT1A1 and increased thyroidal conversion of T4 to T3 via DIO1 were responsible in part for PFOS-induced hypothyroxinemia in rats.