Retene, pyrene and phenanthrene cause distinct molecular-level changes in the cardiac tissue of rainbow trout (Oncorhynchus mykiss) larvae, part 2 – Proteomics and metabolomics

Rigaud, Cyril; Eriksson, Andreas; Rokka, Anne; Skaugen, Morten; Lihavainen, Jenna; Keinänen, Markku; Lehtivuori, Heli; Vehniäinen, Eeva-Riikka

doi:10.1016/j.scitotenv.2020.141161

Cited by 16 publications

(11 citation statements)

References 94 publications

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“…Widespread disruption of structural components within these GO terms may have indicated diminished structural integrity within the embryos, resulting in a wavy notochord. PAHs are known cardiotoxins, with higher molecular weight PAHs typically acting through AHR signaling while lower molecular PAH toxicity is often independent of AHR; however, the widespread disruption of muscle fiber constituents has no precedence among PAHs [ 11 , 48 , 49 ]. The wavy notochord has previously been associated with a few OPAHS, two of which, 2-ethylanthraquinone and 3-hydroxyflouranthene, have parent PAHs measured in the PHSS extracts [ 38 ].…”

Section: Resultsmentioning

confidence: 99%

Coupling Environmental Whole Mixture Toxicity Screening with Unbiased RNA-Seq Reveals Site-Specific Biological Responses in Zebrafish

Rude

Tidwell

Tilton

et al. 2023

Toxics

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Passive sampling device (PSD) extracts paired with developmental toxicity assays in Danio Rerio (zebrafish) are excellent sensors for whole mixture toxicity associated with the bioavailable non-polar organics at environmental sites. We expand this concept by incorporating RNA-Seq in 48-h post fertilization zebrafish statically exposed to PSD extracts from two Portland Harbor Superfund Site locations: river mile 6.5W (RM 6.5W) and river mile 7W (RM 7W). RM 6.5W contained higher concentrations of polycyclic aromatic hydrocarbons (PAHs), but the diagnostic ratios of both extracts indicated similar PAH sourcing and composition. Developmental screens determined RM 6.5W to be more toxic with the most sensitive endpoint being a “wavy” notochord malformation. Differential gene expression from exposure to both extracts was largely parallel, although more pronounced for RM 6.5W. When compared to the gene expression associated with individual chemical exposures, PSD extracts produced some gene signatures parallel to PAHs but were more closely matched by oxygenated-PAHs. Additionally, differential expression, reminiscent of the wavy notochord phenotype, was not accounted for by either class of chemical, indicating the potential of other contaminants driving mixture toxicity. These techniques offer a compelling method for non-targeted hazard characterization of whole mixtures in an in vivo vertebrate system without requiring complete chemical characterization.

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Section: Resultsmentioning

confidence: 99%

Coupling Environmental Whole Mixture Toxicity Screening with Unbiased RNA-Seq Reveals Site-Specific Biological Responses in Zebrafish

Rude

Tidwell

Tilton

et al. 2023

Toxics

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“…UV-irradiation can be rejected as causative agent due to the architecture of the exposure facility (no windows), as the room was illuminated by yellow florescent light. That leaves enzymatic processes and oxidative stress as the most plausible causes; the latter being more likely due the known and established relationship between PAH toxicity and subsequently increased oxidative stress (Timme-Laragy et al 2007 ; Song et al 2019 ), altered iron metabolism (Rigaud et al 2020b ; Eriksson et al 2022b ) and activation of heat shock proteins (Räsänen et al 2012 ) in PAH exposed fish larvae. The body burden of FICZ may also increase when subsequent metabolism by Cyp1a is inhibited (Wincent et al 2012 , 2016 ).…”

Section: Resultsmentioning

confidence: 99%

“…From an aquatic toxicological perspective, the exact mechanisms of toxicity are not fully understood, even after decades of research employing multiple species of fish and types of PAHs (Heintz et al 2000 ; Brinkworth et al 2003 ; Wassenberg and Di Giulio 2004 ; Van Tiem and Di Giulio 2011 ; Clark et al 2013 ; Rigaud et al 2020a ). What is known is that different PAHs induce toxicity through different mechanisms and cause exposure and PAH specific toxicity profiles (Billiard et al 2008 ; Incardona et al 2011 ; Geier et al 2018 ; Rigaud et al 2020a , b ; Eriksson et al 2022a , b ). Additionally, heart structure and function are especially sensitive to the influence of PAH(s) during early life development of fish (Incardona et al 2011 , 2009 ; Vehniäinen et al 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Endogenous AhR agonist FICZ accumulates in rainbow trout (Oncorhynchus mykiss) alevins exposed to a mixture of two PAHs, retene and fluoranthene

et al. 2022

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Multiple studies have reported synergized toxicity of PAH mixtures in developing fish larvae relative to the additive effect of the components. From a toxicological perspective, multiple mechanisms are known to contribute to synergism, such as altered toxicodynamics and kinetics, as well as increased oxidative stress. An understudied contributor to synergism is the accumulation of endogenous metabolites, for example: the aryl hydrocarbon receptor 2 (AhR2) agonist and tryptophan metabolite 6-Formylindolo(3,2-b)carbazole (FICZ). Fish larvae exposed to FICZ, alongside knock-down of cytochrome p450 (cyp1a), has been reported to induced symptoms of toxicity similar to those observed following exposure to PAHs or the dioxin 2,3,7,8-tetrachlorodibenzo-p-dioxin. Here, we explored if FICZ accumulates in newly hatched rainbow trout alevins (Oncorhynchus mykiss) exposed to two PAHs with different properties: retene (potent AhR2 agonist) and fluoranthene (weak AhR2 agonist and Cyp1a inhibitor), either alone or as a binary mixture for 3 and 7 days. We found that exposure to the mixture resulted in accumulation of endogenous FICZ, synergized the blue sac disease index (BSD), and altered the body burden profiles of the PAHs, when compared to the alevins exposed to the individual components. It is thus very plausible that accumulation of endogenously derived FICZ contributed to the synergized BSD index and toxicity in exposed alevins. Accumulation of endogenously derived FICZ is a novel finding that extends our general understanding on PAHs toxicity in developing fish larvae, while at the same time highlighting why environmental risk assessment of PAHs should not be based solely results from the assessment of individual compounds.

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“…In addition, specific effects on the cardiovascular system have been consistently reported following crude oil exposure in fishes ( Incardona et al., 2004 ; Incardona et al., 2005 ; Incardona et al., 2009 ; Adeyemo et al., 2015 ). Recently, a suite of studies ( Incardona et al., 2004 ; Incardona, 2017 ; Incardona et al., 2006 ) suggested low-molecular weight tricyclic PAHs such as phenanthrene (C 14 H 10 ) are largely responsible for the cardiotoxicity associated with crude oil exposure in fishes ( Incardona et al., 2004 ; Incardona, 2017 ; Incardona et al., 2006 ; Brette et al., 2014 ; Brette et al., 2017 ; Rigaud et al., 2020a , b ). Importantly, Incardona et al.…”

Section: Introductionmentioning

confidence: 99%

“…QT prolongation has been linked to human cardiac failure ( Marris et al., 2020a ) and thus assessment of compound potency on erg channel activity or I Kr current density, is a key component of environmental and pharmacological safety testing strategies ( Fermini et al., 2016 ). Phenanthrene is persistent, bioavailable, can readily penetrate membranes and thus can bioaccumulate over time ( Rigaud et al., 2020a , b ; Yin et al., 2007 ; Piazza et al., 2016 ; Zhang et al., 2013 ). For these reasons, phenanthrene is included in the list of priority pollutants by the United States Environmental Protection Agency (US, EPA).…”

Section: Introductionmentioning

confidence: 99%

Phenanthrene alters the electrical activity of atrial and ventricular myocytes of a polar fish, the Navaga cod

2021

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Oil and gas exploration in the Arctic can result in the release of polycyclic aromatic hydrocarbons (PAHs) into relatively pristine environments. Following the recent spill of approximately 17 500 tonnes of diesel fuel in Norilsk, Russia, May 2020, our study focussed on the effects of phenanthrene, a low molecular weight PAH found in diesel and crude oil, on the isolated atrial and ventricular myocytes from the heart of the polar teleost, the Navaga cod ( Eleginus nawaga ). Acute exposure to phenanthrene in navaga cardiomyocytes caused significant action potential (AP) prolongation, confirming the proarrhythmic effects of this pollutant. We show AP prolongation was due to potent inhibition of the main repolarising current, I Kr , with an IC 50 value of ~2 µM. We also show a potent inhibitory effect (~55%) of 1 µM phenanthrene on the transient I Kr currents that protects the heart from early-after-depolarizations and arrhythmias. These data, along with more minor effects on inward sodium (I Na ) (~17% inhibition at 10 µM) and calcium (I Ca ) (~17% inhibition at 30 µM) currents, and no effects on inward rectifier (I K1 and I KAch ) currents, demonstrate the cardiotoxic effects exerted by phenanthrene on the atrium and ventricle of navaga cod. Moreover, we report the first data that we are aware of on the impact of phenanthrene on atrial myocyte function in any fish species.

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Retene, pyrene and phenanthrene cause distinct molecular-level changes in the cardiac tissue of rainbow trout (Oncorhynchus mykiss) larvae, part 2 – Proteomics and metabolomics

Cited by 16 publications

References 94 publications

Coupling Environmental Whole Mixture Toxicity Screening with Unbiased RNA-Seq Reveals Site-Specific Biological Responses in Zebrafish

Coupling Environmental Whole Mixture Toxicity Screening with Unbiased RNA-Seq Reveals Site-Specific Biological Responses in Zebrafish

Endogenous AhR agonist FICZ accumulates in rainbow trout (Oncorhynchus mykiss) alevins exposed to a mixture of two PAHs, retene and fluoranthene

Phenanthrene alters the electrical activity of atrial and ventricular myocytes of a polar fish, the Navaga cod

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