Release and toxicity of adipose tissue-stored TCDD: Direct evidence from a xenografted fat model

Joffin, Nolwenn; Noirez, Philippe; Antignac, Jean‐Philippe; Kim, Min Ji; Marchand, Philippe; Falabrègue, Marion; Bizec, Bruno Le; Forest, Claude; Emond, Claude; Barouki, Robert; Coumoul, Xavier

doi:10.1016/j.envint.2018.10.027

Cited by 21 publications

(11 citation statements)

References 37 publications

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“…The outcomes linked to several regulatory pathways modulated by the AhR appear to be dependent on the mode of exposure and the persistence of the ligand (acute vs chronic activation, persistent vs non-persistent). This concept was also strengthened by the observation that AhR deficiency and chronic AhR activation could lead to similar phenotypes such as liver steatosis and/or fibrosis observed in AhR KO mice and Kyn-or TCDD-treated mice (88,(178)(179)(180)(181). Subsequently, SAhRM are now considered to treat pathologies related to a deficiency or an overactivation of the receptor.…”

Section: Conclusion: the Potential Of Ahr Pathways As Therapeutic Tar...mentioning

confidence: 99%

Aryl Hydrocarbon Receptor and Its Diverse Ligands and Functions: An Exposome Receptor

Larigot

Benoit

Koual

et al. 2022

Annu. Rev. Pharmacol. Toxicol.

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The aryl hydrocarbon receptor (AhR) is a transcriptional factor that regulates multiple functions following its activation by a variety of ligands, including xenobiotics, natural products, microbiome metabolites, and endogenous molecules. Because of this diversity, the AhR constitutes an exposome receptor. One of its main functions is to regulate several lines of defense against chemical insults and bacterial infections. Indeed, in addition to its well-established detoxication function, it has several functions at physiological barriers, and it plays a critical role in immunomodulation. The AhR is also involved in the development of several organs and their homeostatic maintenance. Its activity depends on the type of ligand and on the time frame of the receptor activation, which can be either sustained or transient, leading in some cases to opposite modes of regulations as illustrated in the regulation of different cancer pathways. The development of selective modulators and their pharmacological characterization are important areas of research. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Section: Conclusion: the Potential Of Ahr Pathways As Therapeutic Tar...mentioning

confidence: 99%

Aryl Hydrocarbon Receptor and Its Diverse Ligands and Functions: An Exposome Receptor

Larigot

Benoit

Koual

et al. 2022

Annu. Rev. Pharmacol. Toxicol.

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“…This mixture was selected based on recent published human data identifying these different chemicals as the main representatives of the major classes of POPs constituting the current human exposome. [28][29][30][31][32] After 48 h, the epididymal fat pads (100-150 mg) were collected and grafted under the skin of the back of a second set of uncontaminated male mice (receptor), according to the protocol of Joffin et al 8 following the scheme of one receptor for each donor. This second set results in six groups (three doses Â two exposure times) of eight recipient mice each, leading to a total of 48 animals.…”

Section: Exposure To Popsmentioning

confidence: 99%

“…Nevertheless, some examples have illustrated that this release may happen relatively quickly following their bioaccumulation: for instance, gas chromatography high-resolution mass spectrometry (GC-HRMS) monitoring of a representative POP (2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD]) reveals that it is rapidly released from an exposed grafted AT after only 2 days, and distributed to several other tissues of the host. 8 According to the previous example, it is evident that the release of POPs in other tissues needs to be investigated; therefore, the impact of a pollutant mixture released from endogenous sources on the global metabolism requires to be evaluated, especially for human health. For that purpose, a holistic approach provided by metabolomics will be able to trace the modulations of global metabolic profiles.…”

Section: Introductionmentioning

confidence: 99%

NMR metabolomics study of chronic low‐dose exposure to a cocktail of persistent organic pollutants

Lucas‐Torres,

Caradeuc,

Prieur

et al. 2023

NMR in Biomedicine

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Nowadays, exposure to endocrine‐disrupting chemicals (EDCs), including persistent organic pollutants (POPs), is one of the most critical threats to public health. EDCs are chemicals that mimic, block, or interfere with hormones in the body's endocrine system and have been associated with a wide range of health issues. This innovative, untargeted metabolomics study investigates chronic low‐dose internal exposure to a cocktail of POPs on multiple tissues that are known to accumulate these lipophilic compounds. Interestingly, the metabolic response differs among selected tissues/organs in mice. In the liver, we observed a dynamic effect according to the exposure time and the doses of POPs. In the brain tissue, the situation is the opposite, leading to the conclusion that the presence of POPs immediately gives a saturated effect that is independent of the dose and the duration of exposure studied. By contrast, for the adipose tissues, nearly no effect is observed. This metabolic profiling leads to a holistic and dynamic overview of the main metabolic pathways impacted in lipophilic tissues by a cocktail of POPs.

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“…C57BL/6J mice were provided by the CDTA (Center for Animal Distribution, Typing, and Archiving, CNRS, Orléans, France). Experiments on animals were performed in the animal facilities of CDTA (CNRS, Orléans, France) and subsequently at the animal facility of the BioMed Tech (Campus Saint Germain des Prés, INSERM US36, CNRS UMS2009, Université de Paris, Paris, France) according to previously reported procedures [15]. The European Communities Council directive 2010/63/EU on the protection of the animals were followed for the experiments using animals.…”

Section: Animals and Treatmentmentioning

confidence: 99%

Toxicological effects of 2,3,7,8 tetrachlorodibenzo-p-dioxin on the skeletal muscle of mice during the perinatal period: a metabolomics study

et al. 2022

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Persistent organic pollutants (POPs) accumulate in the organisms due to their hydrophobicity and resistance to xenobiotic metabolism. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is one of most representative POPs. Its pathophysiological effects have been extensively studied on many types of tissues but not on muscles. In this study, female C57BL/6J mouse model was used to analyze the long-term effects of maternal exposure to TCDD during gestation and lactation on the skeletal muscles (soleus, plantaris, and gastrocnemius) of the progeny during adulthood. The effects of re-exposure to TCDD in mice exposed during their development were also characterized. Female C57BL/6J mice were maternally exposed to TCDD or its vehicle (n-nonane in corn oil) and then re-exposed to TCDD or its vehicle at 9 weeks of age. The metabolites in the skeletal muscles were analyzed by gas chromatography–quadrupole time of flight-mass spectrometry (GC–qTOF-MS). Univariate analysis showed significant effects in certain metabolites in the skeletal muscle. It also showed that TCDD exerts a more significant impact on exposure to TCDD at 9 weeks of age than during maternal exposure for the soleus. On the other hand, TCDD exerts a more significant impact on mice maternally exposed to TCDD than at 9 weeks of age for the gastrocnemius. Multivariate analysis showed clear discrimination between the TCDD-exposed mice and the control. This study demonstrates the effects of TCDD observed following maternal exposure; some of them can be reinforced or attenuated by a re-exposure at the adult age, suggesting that the POP which mainly acts through the activation of the AhR leads to metabolic adaptation in the skeletal muscles. The period of exposure was a key factor in our study with TCDD playing a crucial role during the maternal period, as compared to when they were exposed at 9 weeks of age. It was inferred that disruption in amino acid metabolism might lead to a loss in muscle mass which may result in muscular atrophy. Our results also show that the metabolite profiles after perinatal exposure are different in different types of muscles even though they are all classified as skeletal muscles. Therefore, TCDD may affect the organism (specifically different skeletal muscles) in a non-homogenous manner.

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Release and toxicity of adipose tissue-stored TCDD: Direct evidence from a xenografted fat model

Cited by 21 publications

References 37 publications

Aryl Hydrocarbon Receptor and Its Diverse Ligands and Functions: An Exposome Receptor

Aryl Hydrocarbon Receptor and Its Diverse Ligands and Functions: An Exposome Receptor

NMR metabolomics study of chronic low‐dose exposure to a cocktail of persistent organic pollutants

Toxicological effects of 2,3,7,8 tetrachlorodibenzo-p-dioxin on the skeletal muscle of mice during the perinatal period: a metabolomics study

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