13 research outputs found
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A new approach for plasma (xeno)metabolomics based on solid-phase extraction and nanoflow liquid chromatography-nanoelectrospray ionisation mass spectrometry
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The Xenometabolome and Novel Contaminant Markers in Fish Exposed to a Wastewater Treatment Works Effluent
Organisms exposed to wastewater treatment works (WwTW)
effluents
accumulate complex mixtures of xenobiotics but there is a scarcity
of information on the nature and impacts of these chemical mixtures.
We applied metabolomics techniques as a novel approach to identify
xenobiotics and their metabolites (the xenometabolome) that bioconcentrate
in fish exposed to a WwTW effluent. Exposed juvenile rainbow trout
(<i>Oncorhynchus mykiss</i>) accumulated surfactants, naphthols,
chlorinated xylenols, and phenoxyphenols, chlorophenes, resin acids,
mefenamic acid, oxybenzone, and steroidal alkaloids in the bile or
plasma, and there were perturbations in the plasma concentrations
of bile acids and lipids. Exposure of adult roach (<i>Rutilus
rutilus</i>) to 50% or 100% concentrations of the same effluent
resulted in dose-dependent increases in plasma concentrations of xenometabolites
as well as cyprinol sulfate and taurocholic acid, lysophospholipids,
and a decrease in sphingosine levels (a key component of cell membrane
lipids). Our findings reveal the highly complex nature of xenobiotics
accumulating in effluent-exposed fish, and the great potential of
metabolomics for both identifying plasma marker (bio)chemicals for
monitoring exposure to wastewater effluents, and for targeting studies
on potential consequent impacts on fish health
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Distinguishing between the metabolome and xenobiotic exposome in environmental field samples analysed by direct-infusion mass spectrometry based metabolomics and lipidomics
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Metabolomics reveals target and off-target toxicities of a model organophosphate pesticide to roach (rutilus rutilus): implications for biomonitoring
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Bioassay-directed identification of novel antiandrogenic compounds in bile of fish exposed to wastewater effluents
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Effects of Exposure to WwTW Effluents over Two Generations on Sexual Development and Breeding in Roach <i>Rutilus rutilus</i>
Exposure
to environmental estrogens in wastewater treatment works
(WwTW) effluents induces feminized responses in male fish, including
the development of eggs in male testes. However, the impacts on the
offspring of exposed fish are not well understood. In this study,
we examined whether roach (Rutilus rutilus) from mothers that had been exposed to an undiluted WwTW effluent
from early life to sexual maturity had altered susceptibility to gonadal
feminization and an impaired capacity to reproduce. For males from
both WwTW effluent exposed mothers and dilution water exposed mothers,
effluent exposure for up to 3 years and 9 months induced feminized
male gonads, although the intersex condition was relatively mild.
There was no difference in the severity of gonadal feminization in
roach derived from either WwTW effluent exposed or dilution water
exposed mothers. Furthermore, a breeding study revealed that roach
with effluent-exposed mothers reproduced with an equal success as
roach with mothers exposed to clean water. Roach exposed to the effluent
for 3 years in this study were able to reproduce successfully. Our
findings provide no evidence for impacts of WwTW effluent exposure
on reproduction or gonadal disruption in roach down the female germ
line and add to existing evidence that male roach with a mild intersex
condition are able to breed competitively
Metabolomics Reveals Target and Off-Target Toxicities of a Model Organophosphate Pesticide to Roach (Rutilus rutilus): Implications for Biomonitoring
The ability of targeted and nontargeted metabolomics to discover chronic ecotoxicological effects is largely unexplored. Fenitrothion, an organophosphate pesticide, is categorized as a “red list” pollutant, being particularly hazardous to aquatic life. It acts primarily as a cholinesterase inhibitor, but evidence suggests it can also act as an androgen receptor antagonist. Whole-organism fenitrothion-induced toxicity is well-established, but information regarding target and off-target molecular toxicities is limited. Here we study the molecular responses of male roach (Rutilus rutilus) exposed to fenitrothion, including environmentally realistic concentrations, for 28 days. Acetylcholine was assessed in brain; steroid metabolism was measured in testes and plasma; and NMR and mass spectrometry-based metabolomics were conducted on testes and liver to discover off-target toxicity. O-demethylation was confirmed as a major route of pesticide degradation. Fenitrothion significantly depleted acetylcholine, confirming its primary mode of action, and 11-ketotestosterone in plasma and cortisone in testes, showing disruption of steroid metabolism. Metabolomics revealed significant perturbations to the hepatic phosphagen system and previously undocumented effects on phenylalanine metabolism in liver and testes. On the basis of several unexpected molecular responses that were opposite to the anticipated acute toxicity, we propose that chronic pesticide exposure induces an adapting phenotype in roach, which may have considerable implications for interpreting molecular biomarker responses in field-sampled fish
Metabolomics Reveals Target and Off-Target Toxicities of a Model Organophosphate Pesticide to Roach (Rutilus rutilus): Implications for Biomonitoring
The ability of targeted and nontargeted metabolomics to discover chronic ecotoxicological effects is largely unexplored. Fenitrothion, an organophosphate pesticide, is categorized as a “red list” pollutant, being particularly hazardous to aquatic life. It acts primarily as a cholinesterase inhibitor, but evidence suggests it can also act as an androgen receptor antagonist. Whole-organism fenitrothion-induced toxicity is well-established, but information regarding target and off-target molecular toxicities is limited. Here we study the molecular responses of male roach (Rutilus rutilus) exposed to fenitrothion, including environmentally realistic concentrations, for 28 days. Acetylcholine was assessed in brain; steroid metabolism was measured in testes and plasma; and NMR and mass spectrometry-based metabolomics were conducted on testes and liver to discover off-target toxicity. O-demethylation was confirmed as a major route of pesticide degradation. Fenitrothion significantly depleted acetylcholine, confirming its primary mode of action, and 11-ketotestosterone in plasma and cortisone in testes, showing disruption of steroid metabolism. Metabolomics revealed significant perturbations to the hepatic phosphagen system and previously undocumented effects on phenylalanine metabolism in liver and testes. On the basis of several unexpected molecular responses that were opposite to the anticipated acute toxicity, we propose that chronic pesticide exposure induces an adapting phenotype in roach, which may have considerable implications for interpreting molecular biomarker responses in field-sampled fish
Bioassay-Directed Identification of Novel Antiandrogenic Compounds in Bile of Fish Exposed to Wastewater Effluents
The widespread occurrence of feminized male fish downstream of some UK Wastewater Treatment Works (WwTWs) has been associated with exposure to estrogenic and potentially antiandrogenic (AA) contaminants in the effluents. In this study, profiling of AA contaminants in WwTW effluents and fish was conducted using HPLC in combination with <i>in vitro</i> androgen receptor transcription screens. Analysis of extracts of wastewater effluents revealed complex profiles of AA activity comprising 21–53 HPLC fractions. Structures of bioavailable antiandrogens were identified by exposing rainbow trout to a WwTW effluent and profiling the bile for AA activity using yeast (anti-YAS) and mammalian-based (AR-CALUX) androgen receptor transcription screens. The predominant fractions with AA activity in both androgen receptor screens contained the germicides chlorophene and triclosan, and together these contaminants accounted for 51% of the total anti-YAS activity in the fish bile. Other AA compounds identified in bile included chloroxylenol, dichlorophene, resin acids, napthols, oxybenzone, 4-nonylphenol, and bisphenol A. Pure standards of these compounds were active in the androgen receptor screens at potencies relative to flutamide of between 0.1 and 13.0. Thus, we have identified, for the first time, a diverse range of AA chemicals in WwTWs that are bioavailable to fish and which need to be assessed for their risk to the reproductive health of these organisms and other aquatic biota
Molecular Mechanisms of Toxicity of Silver Nanoparticles in Zebrafish Embryos
Silver
nanoparticles cause toxicity in exposed organisms and are
an environmental health concern. The mechanisms of silver nanoparticle
toxicity, however, remain unclear. We examined the effects of exposure
to silver in nano-, bulk-, and ionic forms on zebrafish embryos (<i>Danio rerio</i>) using a Next Generation Sequencing approach
in an Illumina platform (High-Throughput SuperSAGE). Significant alterations
in gene expression were found for all treatments and many of the gene
pathways affected, most notably those associated with oxidative phosphorylation
and protein synthesis, overlapped strongly between the three treatments
indicating similar mechanisms of toxicity for the three forms of silver
studied. Changes in oxidative phosphorylation indicated a down-regulation
of this pathway at 24 h of exposure, but with a recovery at 48 h.
This finding was consistent with a dose-dependent decrease in oxygen
consumption at 24 h, but not at 48 h, following exposure to silver
ions. Overall, our data provide support for the hypothesis that the
toxicity caused by silver nanoparticles is principally associated
with bioavailable silver ions in exposed zebrafish embryos. These
findings are important in the evaluation of the risk that silver particles
may pose to exposed vertebrate organisms