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Geology topics

Jason Tyler Magnuson

Publications and source records attributed to Jason Tyler Magnuson.

At least 19 recordsLinked to original sources

Effects of carbamazepine to visual function in early life stage fish

The frequent detection of pharmaceuticals and personal care products (PPCPs) in the environment raises concern for aquatic systems. Carbamazepine (CBZ), an antiepileptic drug, is among the most detected PPCP globally, with concentrations in surface water exceeding those that induce toxicity to aquatic organisms. Non-targeted transcriptomic profiling was conducted in zebrafish ( Danio rerio ) larvae exposed to 0, 1, 5, 10, or 50 μg/L CBZ from 2 h post fertilization (hpf) through hatching, and then sampled at 48, 72, or 144 hpf. Transcriptomic profiles were annotated and characterized with in silico bioinformatic software to assess top enriched pathways and identify targets of environmentally relevant concentrations of CBZ and anchor molecular effects to higher levels of biological organization. Based on this analysis, CBZ was predicted to impair visual perception and sensory system development. The number of eye saccades, determined with a visually mediated behavioral assay, optokinetic response, was significantly reduced in 144 hpf larvae exposed to concentrations as low as 1 μg/L CBZ. These results indicate that environmentally relevant concentrations of CBZ may target and impact processes involved in visual function in fish.

Environmental Research

Risks of per- and polyfluoroalkyl substance exposure through marine fish consumption

Global food trade expansion has enriched diets worldwide but also heightened concerns about contaminant spread. Per- and polyfluoroalkyl substances (PFAS) can persist in the environment for decades, yet their risks through food trade remain unclear. The global median estimated daily intake (EDI) of C8-PFAS (perfluorooctanoic acid and perfluorooctane sulfonate) (0.023 nanograms per kilograms per day) was mapped from 212 marine fish species, which indicated higher EDIs in North America, Oceania, and Europe. Furthermore, European countries play a pivotal role in C8-PFAS trade flows, markedly reshaping exposure pathways and driving increased exposure in many nations. These dynamics highlight the importance of establishing food-safety regulations and international trade standards. Although perfluorooctane sulfonate hazard index decreased by 72% after its 2009 regulations, unregulated long-chain PFAS continue to pose elevated risks.

Science

Tetrabromobisphenol S (TBBPS) causes non-negligible and multigenerational reproductive toxicity in zebrafish

Tetrabromobisphenol S (TBBPS) is one of the most extensively used brominated flame retardants detected in the environment. Despite its widespread presence, the effects of persistent environmental exposure to TBBPS on the reproductive system remain unclear, raising significant health concerns. Here, using the zebrafish ( Danio rerio ) model, we identified significant intergenerational endocrine disruption and reproductive toxicity induced by TBBPS after a life-cycle (150 days) of parental exposure to environmentally relevant concentrations of TBBPS (0.01, 0.1, 1, 10, and 100 μg/L). TBBPS interfered with hormone levels and the expression of genes within the hypothalamic–pituitary–gonadal (HPG) axis in both F0 males and females, leading to reduced embryo quality. The parental transmission of TBBPS also impacted the endocrine and reproductive systems of the F1 fish, including the increase of gonadotropin-releasing hormone 3 neuron numbers, changes in hormone levels, and a decrease in embryo numbers. F2 fish also displayed endocrine disruption, even in the absence of detectable TBBPS residues, evidenced by altered fertilization rates and vitellogenin levels. Together, our findings show that exposure to environmentally relevant concentrations of TBBPS can induce reproductive toxicity that persists across generations, weakening the endocrine system and early growth in offspring by disrupting the HPG axis. These data provide critical insight into the persistent health risks posed by TBBPS.

Environmental Science & Technology

Perfluorodecanoic acid (PFDA) disrupts immune regulation via the toll-like receptor signaling pathway in zebrafish

As there are a growing number of per- and polyfluoroalkyl substances (PFAS) alternative substitutes applied globally, it remains paramount to characterize their potential health risks. Perfluorodecanoic acid (PFDA) is the most common alternative PFAS detected in the environment; however, its toxic effects and underlying mechanism of action to aquatic biota remains unclear. In this study, we present in vitro evidence of PFDA-induced immunotoxicity and gain insight into underlying molecular mechanisms. PFDA induced immune dysfunction in zebrafish primarily through immunosuppression, apoptosis, and inflammatory response which further cascaded to suppress innate and adaptive immunities, ultimately weaking the ability of larvae to defend against pathogenic infection. PFDA-induced immunotoxicity was driven by a dysregulation in the toll-like receptor (TLR) signaling pathway, which was validated through a cotreatment of PFDA with either a morpholino knockdown or inhibitor of myeloid differentiation factor 88. Comparative toxicity studies were carried out with a subset of other alternative PFAS (PFBA, PFOA, PFNA) and it was found that PFDA posed a greater immunotoxic response than other commonly identified PFAS in the environment. This work identified a major target of PFDA, disrupting immune function through the TLR signaling pathway, while inducing a greater toxic response among other tested PFAS, which provides novel insights into understanding the potential environmental risks of PFAS substitutes.

Environmental Science & Technology

Ecotoxicological effects of crude oil to early life stage Danio rerio: A molecular, morphological and behavioral approach focused on swim bladder development

Proper development and inflation of the swim bladder is essential for swimming and foraging behavior in fish. To characterize the effects of the Brazilian oil spill that occurred between 2019 and 2020 to early life stage fish, the expression of genes involved in swim bladder development were targeted, with biochemical assays, morphology, and behavior assessed. The swim bladder was focused on due to recent findings of being a target of polycyclic aromatic hydrocarbons (PAHs) present in oil. Zebrafish ( Danio rerio ) were exposed to oil water accommodated fractions at concentrations measured following the spill, 1.12–71.8 total PAHs (μg-ΣPAHt L −1 ). Larvae exposed to 4.49 and 17.9 μg-ΣPAHt L −1 had a downregulation in swim bladder development genes hb9 , sox2 , has2 , and elovl1a at 48 hr postfertilization (hpf). Downregulation in these genes was associated with a high frequency of uninflated swim bladders at 96 and 168 hpf, with uninflated swim bladders detected in 100% of 96 to 168 hpf larvae exposed to 35.9 and 71.8 μg-ΣPAHt L −1 . Superoxide dismutase and catalase levels were inhibited in larvae exposed to 1.12 and 2.24 μg-ΣPAHt L −1 , respectively. There was an increase in glutathione-S-transferase and glutathione levels in exposed larvae. Average swimming speed and distance were reduced in larvae exposed to 1.12 μg-ΣPAHt L −1 . This suggests that complex mixtures of PAHs from crude oil can inhibit the transcription of genes involved in swim bladder tissue development and proper swim-up behavior, which may have implications for the viability and success of developing larvae, affecting recruitment.

Environmental Toxicology and Chemistry

Perfluorodecanesulfonate (PFDS) induces innate immune toxicity through the NF-κB pathway in early life stage zebrafish

Perfluorodecanesulfonate (PFDS), a long-chain polyfluoroalkyl substance (PFAS), is widely detected in aquatic environments and increasingly recognized for its environmental persistence and bioaccumulative potential; however, its immunotoxicity remains poorly understood in aquatic biota. In this study, early life stage zebrafish ( Danio rerio ) were exposed to environmentally relevant concentrations of PFDS and PFOS for 120 h to better characterize the adverse effects of PFDS on aquatic organisms. Additionally, the toxicological differences between PFDS and PFOS at the same exposure concentrations were compared, as PFDS is a known substitute for PFOS. PFDS bioaccumulated in zebrafish larvae at environmentally relevant concentrations, which disrupted immune function by altering the number of macrophages and neutrophils, inducing oxidative stress, and dysregulating immune markers such as interleukins and immunoglobulins. Mechanistically, PFDS activated the nuclear factor kappa B (NF-κB) signaling pathway, driving pro-inflammatory cytokine expression and immune dysfunction. Furthermore, the use of a NF-κB morpholino knockdown confirmed the role of the NF-κB pathway in mediating PFDS-induced immunotoxicity. These findings provide the first comprehensive evidence of PFDS-induced immunotoxicity being mediated through NF-κB activation, offering novel insights into the ecological risks of long-chain perfluorosulfonic acids. Notably, PFDS exhibited a stronger immunotoxic response relative to PFOS, indicating that its adverse effects may be more severe. Overall, these findings provide valuable insights for the ecological risk assessment of PFDS and the toxic potential that unregulated PFAS can have to aquatic systems.

Environment International

Incidence of pollution, bioaccumulation, biomagnification, and toxic effects of per- and polyfluoroalkyl substances (PFAS) in aquatic ecosystems: A review

Per- and polyfluoroalkyl substances (PFAS) are persistently accumulated in both environmental media and biological systems, leading to significant toxicological effects. Although research on PFAS has expanded in recent years, systematic reviews on its concentration distribution in aquatic environments and biota, as well as its toxicological effects, remain scarce. Moreover, existing literature lacks systematic analyses of diverse aquatic environments and organisms. This review investigates the contamination levels of PFAS in aquatic environments. It also provides a systematic analysis of bioaccumulation in planktonic, swimming, and benthic organisms, including bioaccumulation factors (BAF), biomagnification factors (BMF), trophic magnification factors (TMF), and biota-sediment accumulation factors (BSAF), and evaluates the potential toxic effects on aquatic ecosystems. This study aims to provide theoretical support for the environmental regulation and management of PFAS. Additionally, it seeks to offer data references and potential research directions for future studies, thereby promoting the advancement of PFAS-related research and policy development.

Aquatic Toxicology

High-throughput screening identifies bisphenol P as a potent cardiotoxin, inducing cardiotoxicity through apoptosis and NF-κB Pathway

The increasing use of plastic additives, particularly bisphenols (BPs), has raised significant concerns about their potential risks to human health, especially during critical developmental stages. In this study, we developed a novel high-throughput toxicity screening platform using zebrafish ( Danio rerio ) to identify and prioritize chemicals with cardiotoxic potential, which is based on multidimensional exposure pathways ranging from environmental to human levels. The platform quantitatively assesses heart rate changes based on multilevel exposure pathways (environmental, ecological, and human), effectively prioritizing the most relevant cardiotoxic compounds with potential health risks. Using this platform, we identified bisphenol P (BPP), a widely used substitute for bisphenol A, as a potent cardiotoxic compound. BPP exposure significantly inhibited heart development and function in zebrafish, inducing abnormal heart morphology, reduced heart rate, cardiac output, and hemodynamic disturbances. Additionally, NF-κB signaling pathway analysis, including morpholino knock-down and inhibitor experiments, confirmed that BPP mediates cardiac toxicity by inducing cardiomyocyte apoptosis. Our findings underscore the toxicity that BP substitutes can have, while highlighting the potential of this multidimensional screening platform in evaluating cardiovascular toxicity and guiding future toxicological assessments during critical developmental windows.

Environmental Science & Technology

Establishment of a cell culture from Daphnia magna as an in vitro model for (eco)toxicology assays: Case study using Bisphenol A as a representative cytotoxic and endocrine disrupting chemical

Bisphenol A (BPA) is a widely used industrial compound found in polycarbonate plastics, epoxy resin, and various polymer materials, leading to its ubiquitous presence in the environment. The toxicity of BPA to aquatic organisms has been well documented following in vivo exposure scenarios, with known cytotoxic and endocrine-disrupting effects. As such, BPA was used in this study as a well-characterized chemical to implement more ethical and resource-efficient scientific practices in toxicity testing through new approach methods (NAMs). Due to the frequent use of Daphnia spp. as a model organism in toxicology, we developed an in vitro cell culture system from Daphnia magna embryos, with optimized medium to support cell longevity. The cultures were maintained for up to two months, demonstrating their stability and suitability for cytotoxicity studies. Using this novel system, lethal concentration 50 (LC 50 ) values were determined at the 24 and 48 h time points following BPA exposure. Subsequently, oxidative stress, endocrine disruption, and DNA damage were assessed through gene expression, activity assays, and a comet assay in BPA-exposed cells. LC 50 values of 52 µM and 20 µM BPA were calculated after 24 and 48 h exposures, respectively. BPA cells exposed to 20 and 52 µM had significantly increased GSH, GPx, and GST activity levels. mRNA expression analysis revealed significant upregulations in the expression of hsp70, hsp90, gst, gpx, vtg1 , and cyp4 , with downregulations of sod, cat , and ecr following BPA exposure. Furthermore, comet assays showed a significantly higher level of DNA damage induced by BPA compared to controls, with greater comet and tail lengths. This study established a novel in vitro Daphnia model, using BPA as a case study for determining toxic effects, further highlighting the importance and applicability of utilizing alternative methods in ecotoxicological research through reducing animal use.

Aquatic Toxicology

Influence of cardiotoxicity on visual function in developing zebrafish ( Danio rerio ) exposed to Deepwater Horizon crude oil

Polycyclic aromatic hydrocarbons (PAHs) are toxic constituents of crude oil that can induce cardiac dysfunction and vision impairment in early life stage (ELS) fishes. However, it is currently unknown whether visual impairments are independent effects or if they result from underlying PAH cardiotoxicity. To better understand this mechanism, microinjection of microRNA 133b (miR133b) was used to impair cardiac development in ELS zebrafish (injected at <1.25 hpf). Vision and cardiac endpoints were compared between miR133b-injected and oil-exposed zebrafish (4–72 hpf, 54.68–60.41 µg/L tPAH 50 ) to determine the influence of cardiac dysfunction and oil exposure on visual function. At 7 dpf, pericardial area and eye area were measured, and visual function was assessed by optokinetic response (OKR). Over 94 % of miR133b larvae and 45 % of oil-exposed larvae exhibited pericardial edema. Across treatments, there was a strong negative linear correlation between pericardial area and eye area ( r =-0.839, p < 0.0001). All miR133b larvae that exhibited pericardial edema and 18 % of the oil-exposed larvae that exhibited pericardial edema also exhibited reduced eye area (microphthalmia). In both the miR133b and oil groups, OKR was significantly reduced in larvae exhibiting pericardial edema ( p < 0.0001) and in larvae exhibiting reduced eye area ( p < 0.0001). A negative binomial generalized linear model (GLM) indicated that reduced eye area ( p < 0.0001), rather than pericardial edema ( p = 0.76), was a significant predictor of OKR. However, pericardial edema was strongly correlated with reduced eye area across treatments. These results suggest that visual effects may result from an interaction of cardiotoxicity as well as direct impacts to the visual system.

Aquatic Toxicology

Amitriptyline and nortriptyline induce ocular toxicity in early life stage zebrafish (Danio rerio)

The global use of antidepressants has steadily increased, raising concern to aquatic ecosystems due to the incomplete removal during wastewater treatment. Tricyclic antidepressants (TCAs) act on the neuronal system by inhibiting the reuptake of serotonin and norepinephrine. However, despite visual function being heavily dependent on the neuronal system, a knowledge gap remains regarding the ocular toxicity of TCAs. To bridge this knowledge gap, zebrafish ( Danio rerio ) embryos were exposed to sublethal test concentrations of amitriptyline (AMI, 0.3 to 300 μg/L nominal, 2.04 to 234 μg/L measured) and nortriptyline (NOR, 0.03 to 300 μg/L nominal, >0.107 to 20.7 μg/L measured), with the lowest test concentrations being environmentally relevant. Visual function was assessed with the optokinetic response assay, eye structure development was assessed histologically, and gene expression changes were analysed via transcriptomic profiling. Larval zebrafish (120 h post fertilization (hpf)) exposed to 4.99 and 234 μg/L of AMI exhibited a 26 % and 86 % decrease in the number of eye saccades respectively, with zebrafish exposed to 20.7 μg/L of NOR exhibiting a 65 % decrease. Histological analysis indicated a significant increase of the retinal pigment epithelium thickness after exposure to 234 μg/L of AMI and 20.7 μg/L of NOR. Transcriptomic analysis resulted in 1207 and 2742 differentially expressed genes across both AMI and NOR treatment groups respectively, including genes involved in vision, synaptic signaling, and neuronal development. These findings demonstrate that sublethal concentrations of AMI and NOR affect early life stage zebrafish visual development, which may be sensitive endpoint that could be incorporated into ecological risk assessments.

Comparative Biochemistry and Physiology Part C: To

Exposure to the Polychlorinated biphenyl mixture Aroclor 1254 elicits neurological and cardiac developmental effects in early life stage zebrafish (Danio rerio)

The goal of this study was to compare the bioaccumulation of the PCB mixture Aroclor 1254 in zebrafish to cardiac and neurologic outcomes. The establishment of effect concentrations (ECs) for cardiac and neurotoxic effects of PCBs in early life stage fish is challenging due to a lack of measured PCB concentrations in test media (e.g., fish tissue), the lack of standard exposure methods, and the propensity of PCBs to adsorb to test glassware and materials resulting in discrepancies in ECs from different studies with similar endpoints. Reporting tissue concentrations in test organisms will allow for standardization across different tests and thus may improve estimations of effect thresholds. Early life stage zebrafish ( Danio rerio ) are a common environmental toxicological model well represented within the literature, making them ideal for comparisons across multiple studies. Embryos were exposed at 6 h post fertilization (hpf) to aqueous Aroclor 1254 for 96 h with or without renewal in addition to a PCB 126 positive control for cardiotoxicity. PCB concentrations were measured in both exposure solutions and tissue samples. Measured concentrations of Aroclor 1254 in test solutions ranged from 8.7% to 870% of nominal concentrations. Heart rate, pericardial edema, and neurological endpoints (eye tremors) were measured in 102 hpf larvae. Pericardial edema was not present in Aroclor 1254-treated zebrafish but was observed in those exposed to PCB-126. Concentration-dependent bradycardia was observed in zebrafish exposed to Aroclor 1254 and PCB-126. Similarly, a concentration-dependent increase in eye tremor behavior was observed in embryos exposed to Aroclor 1254. Data produced by this study demonstrate novel toxicological effects of Aroclor 1254 and highlight the importance of measuring PCBs in both exposure and receptor media.

Chemosphere

Abundance of microplastics in a typical urban wetland in China: Association with occurrence and carbon storage

Microplastics (MPs) are gaining attention for their widespread presence and toxicity in ecosystems. However, their role as a carbon source in urban wetland carbon sinks is still unclear. In this study, the microplastic-carbon (MP-C) was firstly quantified based on the abundance and occurrence characteristics, including MP morphology, size and type in the Sanyang Wetland, a typical urban wetland of China. MP abundances ranged from 2.4 ± 0.6–14.9 ± 1.5 items/L in surface water and 6.6 ± 1.2 × 10 3 to 46.3 ± 5.9 × 10 3 items/kg in sediment. The predominant morphological characterization of MPs was fragments smaller than 200 μm in size, consisting of PP, PE, and PET, which suggests that the main source was domestic wastewater discharge nearby. Notably, in the Sanyang wetland, the contribution of MP-C to total organic carbon (TOC) was estimated to be 0.023 0.20 % in water and 0.026 0.28 % in sediment. With the continuous production of plastics globally, these values were predicted to increase to 0.12 0.71 % and 0.83 4.12 % by 2100, respectively. Although the estimations relied on simplified geometric assumptions for MP volume and theoretical carbon content, these approaches provide a reasonable basis for understanding MP-C dynamics in wetlands under current analytical constraints. The integration of MP-C characterization during environmental monitoring and management strategies would enhance our understanding of MP pollution's role in the carbon cycle.

Journal of Hazardous Materials

Exposure of infants to antibiotics via cord blood, breast milk, and formula: A review on exposure level, temporal variation, and risk assessment

The pervasive use of antibiotics across various sectors, including agriculture, medicine, and aquaculture, has led to a notable increase in environmental antibiotic residues. This phenomenon has raised significant public concern regarding the potential health risks antibiotics may pose, particularly to vulnerable populations such as infants. However, the conceptualization of exposure routes of antibiotics to infants and the associated health risks has not been conducted. This review summarized three main pathways infants are exposed to antibiotics, including umbilical cord blood, breast milk, and infant formula. Antibiotic exposure levels in infants were synthesized, examining spatial and temporal trends in antibiotic concentrations across different media through clinical testing. We also analyzed the doses of antibiotics consumed by infants over time through breast milk and formula, evaluating the associated risks. Furthermore, we explored the potential adverse effects of early-life antibiotic exposure on the infant gut microbiota, physical development, and multiple organ systems. Given the global significance of antibiotic distribution, it is pertinent to comprehensively monitor antibiotic concentrations in infants and conduct longitudinal follow-up studies on their growth and development, accurately quantifying and assessing the impacts on fetal and infant health.

Journal of Hazardous Materials

Metabolomic profiling identifies the mitochondria as a target of pentachlorophenol toxicity in the blood clam (Tegillarca granosa)

The pervasive presence of pentachlorophenol (PCP) in aquatic-benthic ecosystems poses a threat to organisms. However, the toxicological mechanisms of PCP in benthic organisms are limited. In this study, Tegillarca granosa , a representative bivalve species, was treated with environmentally relevant concentrations of PCP (1, 10, and 100 μg/kg) and positive control for 28 days via sediment exposure to investigate bioaccumulation potential, metabolomic profiles, and histopathology. The biota-sediment bioaccumulation factor for PCP was 9.1. Given the capability of PCP to act as an uncoupler of oxidative phosphorylation, studies were performed to determine key events in the adverse outcome pathway associated with this molecular initiating event. Metabolic profiles indicated a disruption in lipid metabolism, as well as imbalances in the quantity of calcium, which was associated with the synthesis of reactive oxygen species (ROS). A reduction in adenosine-5′-triphosphate (ATP) levels were seen in clams treated with PCP and in animals treated with carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP), which served as a positive control. When clams were co-exposed to 100 μg/kg PCP and 500 μg/kg ATP, PCP toxicity was diminished and levels of mitochondrial calcium, as well as ROS, were reduced. These results suggest that mitochondrial impairment is a key event in the toxic mechanism of PCP to T. granosa .

Marine Pollution Bulletin

A universal method for the simultaneous determination of environmental pollutants in marine biological samples: Per- and polyfluoroalkyl substances and antibiotics as a case study

Conventional detection technologies for environmental contaminants have primarily focused on providing accurate qualitative and quantitative evaluations for single pollutant types, leading to increased costs and an inability to satisfy the growing demand for detecting a broader spectrum of pollutants. Here, we introduced a novel analytical method to simultaneously measure the concentration levels of diverse environmental pollutants, characterized by their distinct properties, across complex biological samples. Per- and polyfluoroalkyl substances (PFAS) and antibiotics were used as a case study due to their frequency of detection in the environment and known impacts Our method harnesses the salting-out effect of sodium chloride on proteins within the muscle tissues of 178 marine species, which significantly reduces the addition of extraneous substances, mitigates matrix interference, and avoids reliance on solid-phase extraction or dispersive extraction agents. The method provides a simultaneous pretreatment for the detection of several compounds, with detection limits from 0.002 to 0.41 ng/g dry weight, which are substantially lower than conventional methods. Overall, this method streamlines efficiency, decreases costs, lessens matrix effects, and sets a solid groundwork for future applications in the concurrent detection of a broader spectrum of environmentally pertinent pollutants with varied characteristics.

ACS ES&T Water

Perfluorohexanesulfonic acid (PFHxS) induces hepatotoxicity through the PPAR signaling pathway in larval zebrafish (Danio rerio)

In recent years, the industrial substitution of long-chain per- and polyfluoroalkyl substances (PFAS) with short-chain alternatives has become increasingly prevalent, resulting in the widespread environmental detection of perfluorohexanesulfonic acid (PFHxS), a short-chain PFAS. However, there remains limited information about the potential adverse effects of PFHxS at environmental concentrations to wildlife. Here, early life stage zebrafish ( Danio rerio ) were exposed to environmentally relevant concentrations of PFHxS to better characterize the adverse effects of PFHxS on aquatic organisms. Nontargeted, transcriptomic analysis revealed potential hepatotoxic effects in exposed larvae, including macrovesicular and microvesicular hepatic steatosis, as well as focal liver necrosis. Morphological, histological, biochemical, and targeted transcript expression profiles further confirmed significant alterations in hepatocellular lesion numbers, liver pathological structures, relative liver size, liver biochemical parameters, and liver function genes. To validate the PPAR-mediated toxicological mechanism identified as an enriched pathway through in silico bioinformatics analysis, we tested the coexposure to an antagonist and PPAR morpholino knockdown. This intervention alleviated PFHxS-induced hepatic effects, including reductions in the levels of aspartate aminotransferase, alanine aminotransferase, total cholesterol, and total triglycerides. Our results demonstrate that environmentally relevant concentrations of PFHxS can impair liver development and function in fish, which could have potential risks to aquatic organisms.

Environmental Science & Technology

Perfluorohexanesulfonic acid (PFHxS) impairs lipid homeostasis in zebrafish larvae through activation of PPARα

Perfluorohexanesulfonic acid (PFHxS), an emerging short-chain per- and polyfluoroalkyl substance, has been frequently detected in aquatic environments. Adverse outcome pathway studies have shown that perfluorinated compounds impair lipid homeostasis through peroxisome proliferator activated receptors (PPARs). However, many of these studies were performed at high concentrations and may thus be a result of overt toxicity. To better characterize the molecular and key events of PFHxS to biota, early life-stage zebrafish ( Danio rerio ) were exposed to concentrations detected in the environment (0.01, 0.1, 1, and 10 μg/L). Lipidomic and transcriptomic evaluations were integrated to predict potential molecular targets. PFHxS significantly impaired lipid homeostasis by the dysregulation of glycerophospholipids, fatty acyls, glycerolipids, sphingolipids, prenol lipids, and sterol lipids. Informatic analyses of the lipidome and transcriptome indicated alterations of the PPAR signaling pathway, with downstream changes to retinol, linoleic acid, and glycerophospholipid metabolism. To assess the role of PPARs, potential binding of PFHxS to PPARs was predicted and animals were coexposed to a PPAR antagonist (GW6471). Molecular simulation indicated PFHxS had a 27.1% better binding affinity than oleic acid, an endogenous agonist of PPARα. Antagonist coexposures rescued impaired glycerophosphocholine concentrations altered by PFHxS. These data indicate PPARα activation may be an important molecular initiating event for PFHxS.

Environmental Science & Technology