Adverse Outcome Pathway on aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2

Doering, Jon A.; Hecker, Markus; Villeneuve, Dan; Zhang, Xiaowei

doi:10.1787/bd46b538-en

Cited by 2 publications

(2 citation statements)

References 61 publications

(114 reference statements)

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“…Furthermore, developmental PAH toxicity is Ahr2 dependent, as knockdown of the ahr2, but not cyp1a, has been reported to prevent the formation toxicity in fish larvae (Incardona et al, 2006;Scott et al, 2011). Additional pathways governed by Ahr2 activation, such as cyclooxygenase-2, have also been suggested to contribute PAH mediated toxicity (Adverse Outcome Pathway 21 (Doering et al, 2019)). However, it has to be noted that not every PAH induce toxicity through improper activation of Ahr2.…”

Section: Introductionmentioning

confidence: 99%

“…The few controlled laboratory studies available have reported potentized mixture toxicity relative to the components (Willett et al, 1998;Di Giulio, 2004a, 2004b;Wills et al, 2009;Garner et al, 2013;Geier et al, 2018). This suggests that toxicity is induced through multiple simultaneous mechanisms and processes, all of which contribute to the induction of toxicity (Doering et al, 2019;Meador and Nahrgang, 2019).…”

Section: Introductionmentioning

confidence: 99%

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Changes in Cardiac Proteome and Metabolome Following Exposure to the Pahs Retene and Fluoranthene and Their Mixture in Developing Rainbow Trout Alevins

Eriksson

Rigaud²,

Rokka³

et al. 2022

SSRN Journal

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Changes in Cardiac Proteome and Metabolome Following Exposure to the Pahs Retene and Fluoranthene and Their Mixture in Developing Rainbow Trout Alevins

Eriksson

Rigaud²,

Rokka³

et al. 2022

SSRN Journal

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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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Adverse Outcome Pathway on aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2

Cited by 2 publications

References 61 publications

Changes in Cardiac Proteome and Metabolome Following Exposure to the Pahs Retene and Fluoranthene and Their Mixture in Developing Rainbow Trout Alevins

Changes in Cardiac Proteome and Metabolome Following Exposure to the Pahs Retene and Fluoranthene and Their Mixture in Developing Rainbow Trout Alevins

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

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