Targeted Metabolomic Assessment of the Sub-Lethal Toxicity of Halogenated Acetic Acids (HAAs) to Daphnia magna

Labine, Lisa M.; Simpson, Myrna J.

doi:10.3390/metabo11020100

Cited by 8 publications

(3 citation statements)

References 96 publications

(159 reference statements)

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“…In our experiments, alterations in the TCA cycle, the urea cycle and metabolism of amino acids were highlighted as perturbed with intensity of stress. Although our analysis was a preliminary discovery analysis and not targeted to any pathway, targeted methods have identified perturbations in specific pathways [ 54 ] or mapped these changes on specific tissues [ 55 ] in these crustaceans. Furthermore, this study focused on a composite mixture as a stress pool and not on a specific chemical; however, lithium, for example, has been recently assessed in its nanoparticle form to affect amino acid, starch and glucose metabolism, which could also be reflected in our study from changes in the relevant catabolic enzymes [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

The Effects of Single and Combined Stressors on Daphnids—Enzyme Markers of Physiology and Metabolomics Validate the Impact of Pollution

Michalaki

McGivern²,

Poschet³

et al. 2022

Toxics

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The continuous global increase in population and consumption of resources due to human activities has had a significant impact on the environment. Therefore, assessment of environmental exposure to toxic chemicals as well as their impact on biological systems is of significant importance. Freshwater systems are currently under threat and monitored; however, current methods for pollution assessment can neither provide mechanistic insight nor predict adverse effects from complex pollution. Using daphnids as a bioindicator, we assessed the impact in acute exposures of eight individual chemicals and specifically two metals, four pharmaceuticals, a pesticide and a stimulant, and their composite mixture combining phenotypic, biochemical and metabolic markers of physiology. Toxicity levels were in the same order of magnitude and significantly enhanced in the composite mixture. Results from individual chemicals showed distinct biochemical responses for key enzyme activities such as phosphatases, lipase, peptidase, β-galactosidase and glutathione-S-transferase. Following this, a more realistic mixture scenario was assessed with the aforementioned enzyme markers and a metabolomic approach. A clear dose-dependent effect for the composite mixture was validated with enzyme markers of physiology, and the metabolomic analysis verified the effects observed, thus providing a sensitive metrics in metabolite perturbations. Our study highlights that sensitive enzyme markers can be used in advance on the design of metabolic and holistic assays to guide the selection of chemicals and the trajectory of the study, while providing mechanistic insight. In the future this could prove to become a useful tool for understanding and predicting freshwater pollution.

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Section: Discussionmentioning

confidence: 99%

The Effects of Single and Combined Stressors on Daphnids—Enzyme Markers of Physiology and Metabolomics Validate the Impact of Pollution

Michalaki

McGivern²,

Poschet³

et al. 2022

Toxics

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“…Although PFHxA and PFHxS shared many similarities in their respective metabolic responses, there were also unique secondary responses observed with each pollutant (Figures 2 and 4). Halogenated carboxylic acid–bearing pollutants have been found to perturb purine and TCA cycle pathways in aquatic organisms including D. magna (Berends et al, 1999; Labine et al, 2022; Labine & Simpson, 2021). The polar functionality of PFAS, including carboxylic acid–bearing pollutants such as PFBA, PFHxA, and PFNA, could lead to the formation of hydrogen bonds between the pollutant and nucleotides, impeding the formation of structural hydrogen bonds between other nucleotides and leading to DNA base‐pair mutations (Chou et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Sublethal Exposure of Per‐ and Polyfluoroalkyl Substances of Varying Chain Length and Polar Functionality Results in Distinct Metabolic Responses in Daphnia magna

Labine

Pereira

Kleywegt

et al. 2022

Enviro Toxic and Chemistry

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Per‐ and polyfluoroalkyl substances (PFAS) are a class of persistent organic pollutants used in industrial applications because of their physicochemical properties, which results in their ubiquitous presence across environmental matrices. To date, legacy PFAS have been well studied; however, the concentration of alternative PFAS may exceed the concentration of legacy pollutants, and more information is needed regarding the sublethal toxicity at the molecular level of aquatic model organisms, such as Daphnia magna. Perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorohexanesulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) are four widely detected PFAS alternatives of varying chain length and polar functionality that are quantified in aquatic environments. The present study examines the metabolic perturbations of PFAS with varying chemistries to D. magna using targeted mass spectrometry–based metabolomics. Daphnia were acutely exposed to sublethal concentrations of PFBA, PFHxA, PFHxS, and PFNA before the polar metabolite profile was extracted from single organisms. Multivariate analysis demonstrated significant separation between the sublethal concentrations of PFHxA, PFHxS, and PFNA relative to the controls; in sum, longer chain lengths demonstrated greater overall perturbations to the extracted metabolic profiles. Univariate statistics revealed significant perturbations in the concentrations of several amino acids, nucleotides/nucleosides, and neurotransmitters with exposure to PFAS. These metabolic perturbations are consistent with disruptions in energy metabolism (pantothenate and coenzyme A metabolism, histidine metabolism) and protein synthesis (aminoacyl‐transfer RNA biosynthesis and amino acid metabolism), which were identified through biochemical pathway analysis. These results provide evidence that although PFAS chemistry (chain length and polar functional group) invokes unique metabolic responses, there is also an underlying toxic mode of action that is common with select PFAS exposure. Overall, the present study highlights the capabilities of environmental metabolomics to elucidate the molecular‐level perturbations of pollutants within the same chemical class to model aquatic organisms, which can be used to prioritize risk assessment of substituted PFAS alternatives. Environ Toxicol Chem 2023;42:242–256. © 2022 SETAC

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“…To examine how BPA, BPF and BPS sub-lethal exposure may alter D. magna metabolism, this study used a targeted liquid-chromatography with tandem mass spectrometry (LC-MS/MS) method to compare metabolic responses of BPA with its analogues, BPF and BPS. This method targets polar metabolites, including amino acids, sugar derivatives, carboxylic acids, nucleosides, nucleotides, vitamins, polyamines, and neurotransmitters [50,51]. Previous studies involving D. magna showed that exposure to BPA elicits disruptions to amino acid and energy metabolism pathways [39,40].…”

Section: Introductionmentioning

confidence: 99%

Metabolomics Reveals That Bisphenol Pollutants Impair Protein Synthesis-Related Pathways in Daphnia magna

et al. 2021

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Bisphenols are used in the production of polycarbonate plastics and epoxy resins. Bisphenol A (BPA) has been widely studied and is believed to act as an endocrine disruptor. Bisphenol F (BPF) and bisphenol S (BPS) have increasingly been employed as replacements for BPA, although previous studies suggested that they yield similar physiological responses to several organisms. Daphnia magna is a common model organism for ecotoxicology and was exposed to sub-lethal concentrations of BPA, BPF, and BPS to investigate disruption to metabolic profiles. Targeted metabolite analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to measure polar metabolites extracted from D. magna, which are linked to a range of biochemical pathways. Multivariate analyses and individual metabolite changes showed similar non-monotonic concentration responses for all three bisphenols (BPA, BPF, and BPS). Pathway analyses indicated the perturbation of similar and distinct pathways, mostly associated with protein synthesis, amino acid metabolism, and energy metabolism. Overall, we observed responses that can be linked to a chemical class (bisphenols) as well as distinct responses that can be related to each individual bisphenol type (A, F, and S). These findings further demonstrate the need for using metabolomic analyses in exposure assessment, especially for chemicals within the same class which may disrupt the biochemistry uniquely at the molecular-level.

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Targeted Metabolomic Assessment of the Sub-Lethal Toxicity of Halogenated Acetic Acids (HAAs) to Daphnia magna

Cited by 8 publications

References 96 publications

The Effects of Single and Combined Stressors on Daphnids—Enzyme Markers of Physiology and Metabolomics Validate the Impact of Pollution

The Effects of Single and Combined Stressors on Daphnids—Enzyme Markers of Physiology and Metabolomics Validate the Impact of Pollution

Sublethal Exposure of Per‐ and Polyfluoroalkyl Substances of Varying Chain Length and Polar Functionality Results in Distinct Metabolic Responses in Daphnia magna

Metabolomics Reveals That Bisphenol Pollutants Impair Protein Synthesis-Related Pathways in Daphnia magna

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