Toxicity Of Perfluorooctane Sulfonate Research Articles

Perfluorooctane sulfonate causes HK-2 cell injury through ferroptosis and endoplasmic reticulum stress pathways.

Perfluorooctane sulfonate (PFOS) is a synthetic persistent organic compound that is widely used in industrial products. Studies have shown that PFOS can accumulate in environment and pose a threat to human health. As the kidney is the main excretory organ for PFOS, it is important to study PFOS damage to the kidney to investigate its toxicity. Human proximal tubular epithelial cells (HK-2) were treated with 200μM PFOS or 1μM Fer-1. Cell viability, the levels of MDA, GSH, intracellular iron ion, and GPX-4 were determined. The expression of KIM-1 and endoplasmic reticulum stress (ERS) related proteins were determined. The expression levels of KIM-1, a marker of renal tubular injury, and ERS-related proteins, GRP78, ATF6, IRE1, and PERK, were significantly increased in HK-2 cells exposed to PFOS. The levels of MDA and intracellular total iron ion also were significantly increased in HK-2 cells exposed to PFOS and the levels of GSH and GPX-4 were significantly decreased. PFOS can damage HK-2 cells through ferroptosis and endoplasmic reticulum stress, which provides a theoretical foundation for exploring the toxicity of PFOS to the kidney.

Assessment of cardiotoxicity induced by PFOS exposure and mechanism research via untarget metabolomics

Perfluorooctane sulfonate (PFOS), widely used in various industrial and commercial materials, can accumulate in the human body due to its high environmental stability, and thus potentially has cardiotoxicity. We assess cardiotoxicity through rat exposure to PFOS by intraperitoneal injection. Untargeted metabolomic analysis was used to explore the potential cardiotoxicity mechanism of PFOS. In vivo, PFOS exposure increases pro-inflammatory factors TNF-α and IL-1β and decreases anti-inflammatory factors IL-10 and TGF-β. PFOS exposure causes pathological changes in cardiac tissue and increases cardiac injury markers brain natriuretic peptide (BNP), lactate dehydrogenase (LDH), C-reactive protein (CRP) in serum and triglyceride (TG), total cholesterol (TC) and ox-LDL in plasma. Increased expression of plasminogen activator inhibitor-1 (PAI-1) and CD36 indicates that PFOS exacerbates cardiac fibrosis. Untargeted metabolites analysis revealed 414 small molecule metabolites and 33 metabolites that differed after PFOS exposure, and identified 3 potential metabolic pathways. In conclusion, our study shows the inflammatory reactions involved in PFOS cardiotoxicity, and identifies potential pathways and differential metabolites involved in PFOS toxicity.

The VDAC1 oligomerization regulated by ATP5B leads to the NLRP3 inflammasome activation in the liver cells under PFOS exposure

As a persistent organic pollutant, perfluorooctane sulfonate (PFOS) has a serious detrimental impact on human health. It has been suggested that PFOS is associated with liver inflammation. However, the underlying mechanisms are still unclear. Here, PFOS was found to elevate the oligomerization tendency of voltage-dependent anion channel 1 (VDAC1) in the mice liver and human normal liver cells L-02. Inhibition of VDAC1 oligomerization alleviated PFOS-induced nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome activation. Cytoplasmic membrane VDAC1 translocated to mitochondria was also observed in response to PFOS. Therefore, the oligomerization of VDAC1 occurred mainly in the mitochondria. VDAC1 was found to interact with the ATP synthase beta subunit (ATP5B) under PFOS treatment. Knockdown of ATP5B or immobilization of ATP5B to the cytoplasmic membrane alleviated the increased VDAC1 oligomerization and NLRP3 inflammasome activation. Therefore, our results suggested that PFOS induced NLRP3 inflammasome activation through VDAC1 oligomerization, a process dependent on ATP5B to transfer VDAC1 from the plasma membrane to the mitochondria. The findings offer novel perspectives on the activation of the NLRP3 inflammasome, the regulatory mode on VDAC1 oligomerization, and the mechanism of PFOS toxicity.

Impacts of PFOS, PFOA and their alternatives on the gut, intestinal barriers and gut-organ axis

With the restricted use of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), a number of alternatives to PFOS and PFOA have attracted great interest. Most of the alternatives are still characterized by persistence, bioaccumulation, and a variety of toxicity. Due to the production and use of these substances, they can be detected in the atmosphere, soil and water body. They affect human health through several exposure pathways and especially enter the gut by drinking water and eating food, which results in gut toxicity. In this review, we summarized the effects of PFOS, PFOA and 9 alternatives on pathological changes in the gut, the disruption of physical, chemical, biological and immune barriers of the intestine, and the gut-organ axis. This review provides a valuable understanding of the gut toxicity of PFOS, PFOA and their alternatives as well as the human health risks of emerging contaminants.

Effects of Temperature and Salinity on Perfluorooctane Sulfonate (PFOS) Toxicity in Larval Estuarine Organisms.

Perfluorooctane sulfonate (PFOS) is a persistent contaminant that has been found globally within the environment. Key data gaps exist in the toxicity of PFOS to marine organisms, especially estuarine species that are crucial to the food web: fish, shrimp, and mollusks. This study developed toxicity thresholds for larval estuarine species, including grass shrimp (Palaemon pugio), sheepshead minnows (Cyprinodon variegatus), mysids (Americamysis bahia), and Eastern mud snails (Tritia obsoleta). Multiple abiotic stressors (salinity and temperature) were included as variables in testing the toxicity of PFOS. Acute 96 h toxicity testing under standard test conditions of 25 °C and 20 ppt seawater yielded LC50 values of 0.919 mg/L for C. variegatus, 1.375 mg/L for A. bahia, 1.559 mg/L for T. obsoleta, and 2.011 mg/L for P. pugio. The effects of increased temperature (32 °C) and decreased salinity (10 ppt) varied with test species. PFOS toxicity for the sheepshead minnows increased with temperature but was not altered by decreased salinity. For grass shrimp and mud snails, PFOS toxicity was greater under lower salinity. The combination of higher temperature and lower salinity was observed to lower the toxicity thresholds for all species. These data demonstrate that expanding toxicity testing to include a wider range of parameters will improve the environmental risk assessment of chemical contaminants, especially for species inhabiting dynamic estuarine ecosystems.

In silico biomarker analysis of the adverse effects of perfluorooctane sulfonate (PFOS) exposure on the metabolic physiology of embryo-larval zebrafish

Perfluorooctane sulfonate (PFOS) is a ubiquitous pollutant in global aquatic ecosystems with increasing concern for its toxicity to aquatic wildlife through inadvertent exposures. To assess the likely adverse effects of PFOS exposure on aquatic wildlife inhabiting polluted ecosystems, there is a need to identify biomarkers of its exposure and toxicity. We used an integrated systems toxicological framework to identify physiologically relevant biomarkers of PFOS toxicity in fish. An in silico stoichiometric metabolism model of zebrafish (Danio rerio) was used to integrate available (published by other authors) metabolomics and transcriptomics datasets from in vivo toxicological studies with 5 days post fertilized embryo-larval life stage of zebrafish. The experimentally derived omics datasets were used as constraints to parameterize an in silico mathematical model of zebrafish metabolism. In silico simulations using flux balance analysis (FBA) and its extensions showed prominent effects of PFOS exposure on the carnitine shuttle and fatty acid oxidation. Further analysis of metabolites comprising the impacted metabolic reactions indicated carnitine to be the most highly represented cofactor metabolite. Flux simulations also showed a near dose-responsive increase in the pools for fatty acids and acyl-CoAs under PFOS exposure. Taken together, our integrative in silico results showed dyslipidemia effects under PFOS exposure and uniquely identified carnitine as a candidate metabolite biomarker. The verification of this prediction was sought in a subsequent in vivo environmental monitoring study by the authors which showed carnitine to be a modal biomarker of PFOS exposure in wild-caught fish and marine mammals sampled from the northern Gulf of Mexico. Therefore, we highlight the efficacy of FBA to study the properties of large-scale metabolic networks and to identify biomarkers of pollutant exposure in aquatic wildlife.

Exposure to polystyrene microplastics and perfluorooctane sulfonate disrupt the homeostasis of intact planarians and the growth of regenerating planarians

Microplastics (MPs) and perfluorinated compounds (PFAS) are widespread in the global ecosystem. MPs have the ability to adsorb organic contaminants such as perfluorooctane sulfonate (PFOS), leading to combined effects. The current work aims to explore the individual and combined toxicological effects of polystyrene (PS) and PFOS on the growth and nerves of the freshwater planarian (Dugesia japonica). The results showed that PS particles could adsorb PFOS. PS and PFOS impeded the regeneration of decapitated planarians eyespots, whereas the combined treatment increased the locomotor speed of intact planarians. PS and PFOS caused significant DNA damage, while co-treatment with different PS concentrations aggravated and attenuated DNA damage, respectively. Further studies at the molecular level have shown that PS and PFOS affect the proliferation and differentiation of neoblasts in both intact and regenerating planarians, alter the expression levels of neuronal genes, and impede the development of the nervous system. PS and PFOS not only disrupted the homeostasis of intact planarians, but also inhibited the regeneration of decapitated planarians. This study is the first to assess the multiple toxicity of PS and PFOS to planarians after combined exposure. It provides a basis for the environmental and human health risks of MPs and PFAS.

Influence of humic acid on the bioaccumulation, elimination, and toxicity of PFOS and TBBPA co-exposure in Mytilus unguiculatus Valenciennes

Tetrabromobisphenol A (TBBPA) and Perfluorooctane sulfonate (PFOS) are emerging contaminants which coexist in marine environments, posing significant risks to ecosystems and human health. The behavior of these contaminants in the presence of dissolved organic matter (DOM), specifically the co-contamination of TBBPA and PFOS, is not well understood. The bioaccumulation, distribution, elimination, and toxic effects of TBBPA and PFOS on thick-shell mussels (Mytilus unguiculatus V.), with the absence and presence of humic acid (HA), a typical DOM, were studied. The results showed that the uptake of TBBPA decreased and the uptake of PFOS increased when exposed to 1 mg/L HA. However, at higher concentrations of HA (5 and 25 mg/L), the opposite effect was observed. Combined exposure to HA, TBBPA, and PFOS resulted in oxidative stress in the digestive gland, with the severity of stress dependent on exposure time and HA dose. Histological analysis revealed a positive correlation between HA concentration and tissue damage caused by TBBPA and PFOS. This study provides insights into the influence of HA on the bioaccumulation-elimination patterns and toxicity of TBBPA and PFOS in marine bivalves, offering valuable data for ecological and health risk assessments of combined pollutants in aquatic environments rich in DOM.

Combined exposure with microplastics increases the toxic effects of PFOS and its alternative F-53B in adult zebrafish

Microplastics (MPs) can adsorb and desorb organic pollutants, which may alter their biotoxicities. Although the toxicity of perfluorooctane sulfonate (PFOS) and its alternative 6:2 chlorinated polyfluorinated ether sulfonate (F-53B) to organisms has been reported, the comparative study of their combined toxic effects with MPs on aquatic organisms is limited. In this study, adult female zebrafish were exposed to 10 μg/L PFOS/F-53B and 50 μg/L MPs alone or in combination for 14 days to investigate their single and combined toxicities. The results showed that the presence of MPs reduced the concentration of freely dissolved PFOS and F-53B in the exposure solution but did not affect their bioaccumulation in the zebrafish liver and gut. The combined exposure to PFOS and MPs had the greatest impact on liver oxidative stress, immunoinflammatory, and energy metabolism disorders. 16S rRNA gene sequencing analysis revealed that the combined exposure to F-53B and MPs had the greatest impact on gut microbiota. Functional enrichment analysis predicted that the alternations in the gut microbiome could interfere with signaling pathways related to immune and energy metabolic processes. Moreover, significant correlations were observed between changes in gut microbiota and immune and energy metabolism indicators, highlighting the role of gut microbiota in host health. Together, our findings demonstrate that combined exposure to PFOS/F-53B and MPs exacerbates liver immunotoxicity and disturbances in energy metabolism in adult zebrafish compared to single exposure, potentially through dysregulation of gut microbiota.

Increased Perfluorooctanesulfonate (PFOS) Toxicity and Accumulation Is Associated with Perturbed Prostaglandin Metabolism and Increased Organic Anion Transport Protein (OATP) Expression.

Perfluorooctanesulfonate (PFOS) is a widespread environmental pollutant with a long half-life and clearly negative outcomes on metabolic diseases such as fatty liver disease and diabetes. Male and female Cyp2b-null and humanized CYP2B6-transgenic (hCYP2B6-Tg) mice were treated with 0, 1, or 10 mg/kg/day PFOS for 21 days, and surprisingly it was found that PFOS was retained at greater concentrations in the serum and liver of hCYP2B6-Tg mice than those of Cyp2b-null mice, with greater differences in the females. Thus, Cyp2b-null and hCYP2B6-Tg mice provide new models for investigating individual mechanisms for PFOS bioaccumulation and toxicity. Overt toxicity was greater in hCYP2B6-Tg mice (especially females) as measured by mortality; however, steatosis occurred more readily in Cyp2b-null mice despite the lower PFOS liver concentrations. Targeted lipidomics and transcriptomics from PFOS-treated Cyp2b-null and hCYP2B6-Tg mouse livers were performed and compared to PFOS retention and serum markers of toxicity using PCA. Several oxylipins, including prostaglandins, thromboxanes, and docosahexaenoic acid metabolites, are associated or inversely associated with PFOS toxicity. Both lipidomics and transcriptomics indicate PFOS toxicity is associated with PPAR activity in all models. GO terms associated with reduced steatosis were sexually dimorphic with lipid metabolism and transport increased in females and circadian rhythm associated genes increased in males. However, we cannot rule out that steatosis was initially protective from PFOS toxicity. Moreover, several transporters are associated with increased retention, probably due to increased uptake. The strongest associations are the organic anion transport proteins (Oatp1a4-6) genes and a long-chain fatty acid transport protein (fatp1), enriched in female hCYP2B6-Tg mice. PFOS uptake was also reduced in cultured murine hepatocytes by OATP inhibitors. The role of OATP1A6 and FATP1 in PFOS transport has not been tested. In summary, Cyp2b-null and hCYP2B6-Tg mice provided unique models for estimating the importance of novel mechanisms in PFOS retention and toxicity.

Perfluorooctane sulfonate (PFOS) induces apoptosis and autophagy by inhibition of PI3K/AKT/mTOR pathway in human granulosa cell line KGN

Perfluorooctane sulfonate (PFOS) is recognized as an environmental endocrine disruptor with widespread use in industrial manufacturing and daily life, contributing to various public health concerns. However, the precise impacts of PFOS on the ovary and its regulatory mechanisms remain unclear. This study aims to delineate the ovarian toxicity of PFOS and scrutinize its effects on apoptosis and autophagy through modulation of the PI3K/AKT/mTOR pathway in the human granulosa cell line (KGN). Cell viability, assessed via the Cell Counting Kit-8 (CCK8), revealed a dose-dependent reduction in cell viability upon PFOS exposure. Flow cytometry analysis demonstrated an elevated proportion of apoptotic cells following PFOS treatment. Western blot analyses unveiled increased expression of Bax, Cyt c, cleaved caspase-9, and LC3-II/I, coupled with decreased expression of Bcl-2 and p62. Transmission electron microscopy (TEM) observations illustrated a heightened number of autophagosomes induced by PFOS. Molecular docking investigations, in conjunction with Western blot experiments, substantiated PFOS's significant inhibition of the PI3K/AKT/mTOR signaling pathway. These findings collectively underscore that PFOS induces apoptosis and autophagy in KGN cells through modulation of the PI3K/AKT/mTOR pathway, providing experimental evidence for PFOS-induced ovarian toxicity and elucidating the underlying regulatory mechanisms in KGN cells.

Establishing Chronic Toxicity Effect Levels for Zebrafish (Danio rerio) Exposed to Perfluorooctane Sulfonate.

Zebrafish (Danio rerio) are among the aquatic species most sensitive to perfluorooctane sulfonate (PFOS). Environmental regulatory agencies and researchers use effect benchmarks from laboratory zebrafish PFOS toxicity studies in PFOS-spiked water to calculate PFOS aquatic life criteria. Threshold values as low as 0.7 µg/L (identified in an early, limited scope study) have been used in criteria derivation and site-specific aquatic ecological risk assessments. The present study reviews PFOS effects benchmarks for lethality, growth, and reproduction endpoints from more than 20 zebrafish toxicity studies, including a recent multigenerational study conducted by the United States Army Corps of Engineers Engineer Research & Development Center. Our review of 12 key studies examining long-term, chronic exposures (including multigenerational exposures of 300 days or more) indicated that 0.7 µg/L should not be used as a conservative screening threshold given that effects could not be repeated at this concentration by the recent enhanced multigenerational study. Based on this finding and multiple chronic sublethal studies on PFOS in zebrafish, chronic effects on lethality, growth, and reproduction occur at concentrations two orders of magnitude higher than 0.7 µg/L. Overall, the present review indicates a no-effect screening level of 31 µg/L and a low-effect screening level of 96 µg/L should be used to develop PFOS aquatic life criteria and to inform site-specific ecological risk assessments that are charged with evaluating risks to freshwater fish. Environ Toxicol Chem 2024;43:7-18. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Unraveling the mechanism of quercetin alleviating perfluorooctane sulfonate-induced apoptosis in grass carp (Ctenopharyngodon idellus) hepatocytes: AMPK/mTOR-mediated mitophagy

Exposure to persistent new organic pollutants in the environment often leads to high mortality and causes serious economic losses to the aquaculture industry. Currently, perfluorooctane sulfonate (PFOS) is persistent and bio-accumulative in the environment, causing potential risks to aquatic ecosystems, but its toxicity mechanism to aquatic organisms is still unclear. As a natural flavonoid compound, quercetin (QU) has many biological activities such as anti-oxidation, anti-inflammatory, anti-apoptosis and immune regulation. Whether it can be used as a candidate medicine to alleviate PFOS toxicity needs to be further explored. Therefore, in this study, we treated (Ctenopharyngodon idellus) grass carp hepatocytes (L8824) with PFOS (200 μM) and/or QU (60 μM) for 24 h. The results showed that PFOS significantly increased the release of LDH and active oxygen (ROS) in L8824 cells, and led to the decrease of mitochondrial membrane potential (ΔΨm) and ATP content, the increase of mitochondrial ROS, the disorder of mitochondrial dynamics, and the initiation of Bcl-2/Bax-mediated apoptosis. Surprisingly, QU can alleviate the above PFOS-induced grass carp hepatocyte toxicity. In addition, in order to further explore the protective mechanism of QU, we used the molecular docking to predict the binding site between QU and AMPK, and found that there was a high binding capacity between QU and AMPK. In addition, we used Compound C (CC) and 3-Methyladenine (3-MA) to intervene. The results showed that CC and 3-MA intervention aggravated mitochondrial dysfunction and apoptosis factor expression in the QU+PFOS group. These data indicate that PFOS induces oxidative stress, mitochondrial dysfunction, and apoptosis. The regulation of AMPK/mTOR mediated mitophagy by QU may be a new therapeutic strategy to alleviate the hepatotoxicity of PFOS grass carp. This study provides theoretical basis and reference for exploring the toxic mechanism and biological toxic effects of PFOS, and provides a scheme for improving the economic benefits of aquaculture.

The interaction of perfluorooctane sulfonate with hemoproteins and its relevance to molecular toxicology

Perfluorooctane sulfonate (PFOS), a representative of perfluorinated compounds in industrial and commercial products, has posed a great threat to animals and humans via environmental exposure and dietary consumption. Herein, we investigated the effects of PFOS binding on the redox state and stability of two hemoproteins (hemoglobin (Hb) and myoglobin (Mb)). Fluorescence spectroscopy, circular dichroism and UV–vis absorption spectroscopy demonstrated that PFOS could induce the conformational changes of proteins along with the exposure of heme cavity and generation of hemichrome, which resulted in the increased release of free hemin. After that, free hemin liberated from hemoproteins led to reactive oxygen species formation, lipid peroxidation, cell membrane damage and loss of cell viability in vascular endothelial cells, while neither Hb nor Mb did show cytotoxicity. Chemical inhibitors of ferroptosis effectively mitigated hemin-caused toxicity, identifying the hemin-dependent ferroptotic cell death mechanisms. These data demonstrated that PFOS posed a potential threat of toxicity through a mechanism which involved its binding to hemoproteins, decreased oxygen transporting capacity, and increased hemin release. Altogether, our findings elucidate the binding mechanisms of PFOS with two hemoproteins, as well as possible risks on vascular endothelial cells, which would have important implications for the human and environmental toxicity of PFOS.

Meta-Analysis Comparing Nominal and Measured Concentrations of Perfluorooctanoic Acid and Perfluorooctane Sulfonate in Aquatic Toxicity Studies Across Various Experimental Conditions.

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are among the most frequently detected chemicals among the per- and polyfluoroalkyl substances in aquatic environments. Because of their high detection frequency, persistence, and potential toxicity, interest in both PFOA and PFOS has increased in recent years. However, a substantial number of PFOA and PFOS toxicity tests only report nominal, or unmeasured, treatment concentrations, which may complicate the determination of protective values. In addition, previous literature has indicated that differences between nominal and measured concentrations of both PFOA and PFOS could be linked to experimental conditions (e.g., feeding regimes for test organisms, test vessel material [glass or plastic], use of solvent, and the presence of substrate). Therefore, this critical review examined whether nominal and measured concentrations were in close agreement with each other among the current PFOA and PFOS aquatic toxicity literature and if experimental conditions were associated with any observed differences. Nominal and measured concentrations in the current PFOA and PFOS aquatic toxicity literature generally displayed a high degree of linear correlation and relatively low median percent differences. Correlations between measured and nominal concentrations were >0.98 for PFOA and >0.95 for PFOS in freshwater tests across experimental conditions. For saltwater tests, correlations of >0.84 were observed for PFOA and PFOS (separate and combined) across experimental conditions. While measured PFOA and PFOS toxicity tests are generally preferred, the present meta-analysis demonstrated that experimental conditions had little influence on observed discrepancies between nominal and measured concentrations, with the exception of PFOS saltwater tests and PFOA and PFOS freshwater studies that contained substrate. Unmeasured tests with these conditions should be considered carefully based on project needs, with the caveat that the data sets for these two experimental conditions were limited. Environ Toxicol Chem 2023;42:2289-2301. Published 2023. This article is a U.S. Government work and is in the public domain in the USA.

Comparative stress response assessment of PFOS and its alternatives, F-53B and OBS, in wheat: An insight of toxic mechanisms and relative magnitudes

Emerging alternatives to perfluorooctane sulfonate (PFOS), including 6:2 chlorinated polyfluorinated ether sulfonate (F-53B) and p-perfluorous nonenoxybenzene sulfonate (OBS), have been widely detected in the real environment as PFOS restriction. However, the toxicity in plants and the underlying mechanism of F-53B and OBS remain scarce, especially compared to PFOS. PFOS and their emerging alternatives pose significant potential risks to food, especially for crops, safety and human health with the great convenience of high chemical stability. Germination toxicity, oxidative stress biomarkers, and metabolomics were used to compare the relative magnitudes of toxicity of PFOS and its alternatives in wheat (Triticum aestivum L.). PFOS, F-53B, and OBS inhibited wheat germination compared to the control group, with germination inhibition rates of 45.6%, 53.5%, and 64.3% at 400 μM PFOS, F-53B, and OBS exposure, respectively. Moreover, oxidative stress biomarker changes were observed in PFOS, F-53B, and OBS, with OBS being more pronounced. The chlorophyll concentrations in wheat shoots increased, and the anthocyanin concentration decreased along with the increased exposure concentration. Superoxide dismutase (SOD) activity increased in wheat root but decreased in the shoot. Peroxidase (POD) activity and malondialdehyde (MDA) concentration increased, whereas catalase (CAT) activity decreased. Regarding metabolomics, PFOS, F-53B, and OBS exposure (10 μM) significantly altered 85, 133, and 134 metabolites, respectively. According to KEGG enrichment analysis, F-53B specifically affects lipid metabolism, whereas OBS causes an imbalance in amino acid and carbohydrate metabolism. These findings suggested that PFOS, F-53B, and OBS have distinct toxic mechanisms. Thus, our results indicated that the relative size of the toxicity in wheat is as follows: OBS > F-53B > PFOS, and this finding provides a new reference basis for the phytotoxicity assessment of F-53B and OBS.

Efflux transport proteins of Tetrahymena thermophila play important roles in resistance to perfluorooctane sulfonate exposure

The biotoxicity of perfluorooctane sulfonate (PFOS) has been a concern. However, the effects of PFOS on Tetrahymena thermophila, a unicellular model organism, remain unclear. This study aimed to investigate the toxicity and detoxification mechanism of PFOS in this protozoan. PFOS did not show prominent toxic effects on T. thermophila. Cell viability of T. thermophila can be concentration-dependently increased by PFOS. PFOS also increased the stability of cell membranes and the activity of lysosomes. However, PFOS inhibited efflux transporter activities. Most of the PFOS amount remained in the culture medium during the culture periods. Only a low amount of PFOS was absorbed by cells, where PFOS molecules were mainly combined with membrane proteins. The expressions of four membrane protein genes involved in transporting xenobiotics were analyzed by real time-PCR. The gene abcg25 was significantly up-regulated. The growth of abcg25 gene knockout protozoans under PFOS treatment was slightly inhibited. However, the amount of PFOS adsorbed by the knockout protozoans showed no significant difference from the Wild-type protozoans. We concluded that the ABCG25 protein might play a key role in preventing PFOS from entering the cell or being exported from the cells to protect T. thermophila against PFOS. However, ABCG25 was not the only membrane protein able to bind with PFOS.

Ecological effects and molecular mechanisms of single and coexisting PFOS and Cu exposure on submerged macrophytes and periphytic biofilms in aquatic environments

Perfluorooctane sulfonate (PFOS) is an accumulative emerging persistent organic pollutant that coexists with copper (Cu) in aquatic environments and is a severe threat to human health. PFOS has genotoxicity, male reproductive toxicity, neurotoxicity, developmental toxicity and endocrine disrupting effects, and is considered to be a kind of environmental pollutant with systemic multi-organ toxicity. However, the combined effects of PFOS and Cu on aquatic organisms have not been analyzed previously. In this study, we investigate the response of Vallisneria Natans (V. natans) and biofilms to single and combined treatments of PFOS and Cu at environmental concentrations (1.0, 10.0, and 100.0 μg·L−1). Results indicate that single and combined treatment triggered the reactive oxygen species (ROS) metabolism with increased activities of GSH, MDA, CAT, TSOD and an antagonistic joint toxicity. Meanwhile, transcriptomic analyses showed that the peroxidase (PER), 9 glutaredoxin (GRX), and 39 glutathione S-transferase (GST) expression of genes related to ROS detoxification was up-regulated. In addition, single and combined exposure induced the up-regulation of the transport channel genes which encode aquaporins, rapid-type anion channels, and copper-exporting P-type ATPase transporters, promoting the uptake of PFOS and Cu in V. natans, Enhancing detoxification and mitigating the effects of Cu and PFOS exposure. Moreover, PFOS and Cu changed the structural characteristics of extracellular polysaccharides in biofilms, synthesizing large amounts of β-D-glucopyranose PS, α-D-glucopyranose PS. And the community diversity and species evenness changed, with Rhizobiaceae, Chloroplast, and Weeksellaceae being the dominant phylum. This study provides insights into the molecular mechanism of joint toxicity of PFOS and Cu by Transcriptomics and PCR analysis on the submerged macrophyte and their periphyton biofilms.

Early life exposure to low-dose perfluorooctane sulfonate disturbs gut barrier homeostasis and increases the risk of intestinal inflammation in offspring

Perfluorooctane sulfonate (PFOS), one of the legacy per- and poly-fluoroalkyl substances (PFAS), is associated with multiple adverse health effects on children. However, much remains to be known about its potential impacts on intestinal immune homeostasis during early life. Our study found that PFOS exposure during pregnancy in rats significantly increased the maternal serum levels of interleukin-6 (IL-6) and zonulin, a gut permeability biomarker, and decreased gene expressions of Tight junction protein 1 (Tjp1) and Claudin-4 (Cldn4), the tight junction proteins, in maternal colons on gestation day 20 (GD20). Being exposed to PFOS during pregnancy and lactation in rats significantly decreased the body weight of pups and increased the offspring's serum levels of IL-6 and tumor necrosis factor-α (TNF-α) on postnatal day 14 (PND14), and induced a disrupted gut tight junction, manifested by decreased expressions of Tjp1 in pup's colons on PND14 and increased pup's serum concentrations of zonulin on PND28. By integrating high-throughput 16S rRNA sequencing and metabolomics, we demonstrated that early-life PFOS exposure altered the diversity and composition of gut microbiota that were correlated with the changed metabolites in serum. The altered blood metabolome was associated with increased proinflammatory cytokines in offspring. These changes and correlations were divergent at each developmental stage, and pathways underlying immune homeostasis imbalance were significantly enriched in the PFOS-exposed gut. Our findings provide new evidence for the developmental toxicity of PFOS and its underlying mechanism and explain in part the epidemiological observation of its immunotoxicity.

Multiple toxicity evaluations of perfluorooctane sulfonate on intact planarian Dugesia japonica

Perfluorooctane sulfonate (PFOS) is gaining widespread attention as a persistent organic pollutant with multiple mechanisms of toxicity. In this study, PFOS at different concentrations and different exposure times was used to evaluate the multiple toxicities on intact planarian Dugesia japonica. The proliferation of neoblasts, apoptosis,DNA damage and the expression levels of neuronal genes and the major genes of the Wnt pathway were effectively studied. The results demonstrated that the balance between proliferation and apoptosis of intact planarian cells was disrupted after PFOS exposure, which in turn affected tissue homeostasis and differentiation. PFOS exposure led to increased DNA damage and altered neuronal gene expression. In addition, PFOS exposure could down-regulate the expression of Wnt pathway genes, but the inhibition of the Wnt pathway by PFOS was time- and concentration-dependent. These findings suggest that PFOS has multiple toxic effects on planarians and may interfere with cell proliferation and neurodevelopment by affecting the key gene expression in the Wnt pathway, providing estimable information on the neurodevelopmental toxicity and ecotoxicity of PFOS toxicity in aquatic animals and environments.