2020
DOI: 10.1016/j.envpol.2020.114966
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In vitro differential responses of rat and human aryl hydrocarbon receptor to two distinct ligands and to different polyphenols

Abstract: TCDD (2,3,7, and several other environment/food-borne toxic compounds induce their toxicity via the aryl hydrocarbon receptor (AhR). AhR is also modulated by various endogenous ligands e.g. highly potent tryptophan (Trp)-derivative FICZ (6-formylindolo[3,2-b]carbazole) and natural ligands abundant in the human diet e.g. polyphenols. Therefore, evaluating AhR species-specific responses is crucial for understanding AhR physiological functions, establishing risk assessments, and exploring the applicability of AhR… Show more

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Cited by 10 publications
(8 citation statements)
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“…Some compounds are also reported to show species differences in CYP1A1 inhibition (Westerink et al, 2008;Watanabe et al, 2020). On the other hand, the AHR-activating potency of FICZ is reported to be similar in rats and humans (Doan et al, 2020), and the AHR response to exogenous ligands is generally considered to vary little between species. From these facts, it will be of great interest to further investigate whether a compound showing species differences in CYP1A1 inhibition may show species differences in hepatotoxicity caused by this mechanism.…”
Section: Discussionmentioning
confidence: 99%
“…Some compounds are also reported to show species differences in CYP1A1 inhibition (Westerink et al, 2008;Watanabe et al, 2020). On the other hand, the AHR-activating potency of FICZ is reported to be similar in rats and humans (Doan et al, 2020), and the AHR response to exogenous ligands is generally considered to vary little between species. From these facts, it will be of great interest to further investigate whether a compound showing species differences in CYP1A1 inhibition may show species differences in hepatotoxicity caused by this mechanism.…”
Section: Discussionmentioning
confidence: 99%
“…Indeed, an exacerbated cellular response of AhR such as the one exerted by persistent organic pollutants, and particularly dioxinlike compounds, is associated with the triggering of toxicity pathways and affects the transcriptome in a distinct way [138]. Meanwhile, transient but commonly potent AhR activation is induced by endogenous ligands such as the well-studied tryptophan derivative FICZ [139]. This last one is probably the form of interaction of microbial metabolites with AhR due to the physiological machinery regulating their production and degradation in the biological context.…”
Section: Ahr Transcriptional Activation Representing Host-microbe Int...mentioning
confidence: 99%
“…The aryl hydrocarbon receptor (AhR), originally discovered as a xenobiotic receptor involved in upregulating metabolic enzymes, has become increasingly linked to physiological processes (McMillan and Bradfield, 2007;Okey, 2007;Abel and Haarmann-Stemmann, 2010;Wang et al, 2017;Roman et al, 2018;Rothhammer and Quintana, 2019). The discovery of endogenous, dietary and bacterial-derived ligands for the AhR further supports its involvement in the homeostatic regulation of biological processes (Adachi et al, 2001;Denison et al, 2011;Bessede et al, 2014;Faber et al, 2018;Rannug and Rannug, 2018;Doan et al, 2020). Yet, dysregulation of many of these processes can lead to disease states involving the immune system.…”
Section: Role Of the Aryl Hydrocarbon Receptor In Immune Modulationmentioning
confidence: 99%