toxicogenomics

Food toxicology

In the context of the ToxAlim INRA research unit, I contributed to several research projects aiming at understanding the mechanisms and impacts of different food contaminants.

I managed with Thierry Pineau (2008-2009) and then H Guillou (2010-2011) the team that became in 2010 the group of Integrative Toxicology & Metabolism and then I developed and led the GeT-TRiX transcriptomic facility (2011-2015). During these years I supervised the work of 3 PhD students: Alexandre Eveillard (with T. Pineau), Béatrice Roques (with C. Viguié) and Nabila Moussaoui (with H. Houdeau) and contributed to significant projects, including:

DEHP activates CAR and PPARalpha

  • With Béatrice Roques, we studied the pathways by which fipronil, a very common phenylpyrazole insecticide, alters thyroid hormone homeostasis (Roques et al., Tox Sci, 2012). We found that liver metabolic pathways involved in both xenobiotic and thyroid hormone metabolism were activated upon fipronil exposure and that the nuclear receptors CAR and PXR were involved in regulating the expression of the corresponding genes (Roques et al., Biochem Pharmacol, 2013).

Fipronil and TH metabolism

  • Largely based on transcriptomic approaches, the work of A. Marmugi (advisor L Lakhal) allowed us to reveal non-monotonic effects of low doses of bisphenol A on liver gene expression and lipid storage (Marmugi et al., Hepatology, 2013).

Effect of low BPA doses on the liver

These studies, as well as those listed below, provided important insights into the mechanisms and effects of several food contaminants, sometimes contributing directly to the assessement of the toxicity of these substances by regulatory agencies.

Publications

(2015). Changes in intestinal glucocorticoid sensitivity in early life shape the risk of epithelial barrier defect in maternal-deprived rats.. PLoS One. 2014 Feb 20;9(2):e88382..

Project PubMed

(2014). Adverse effects of long-term exposure to bisphenol A during adulthood leading to hyperglycaemia and hypercholesterolemia in mice.. Toxicology. 2014 Nov 5;325:133-43..

Project PubMed

(2012). CYP450-dependent biotransformation of the insecticide fipronil into fipronil sulfone can mediate fipronil-induced thyroid disruption in rats.. Toxicol Sci. 2012 May;127(1):29-41..

Project PubMed

(2012). Low doses of bisphenol A induce gene expression related to lipid synthesis and trigger triglyceride accumulation in adult mouse liver.. Hepatology. 2012 Feb;55(2):395-407..

Project PubMed

(2012). P-glycoprotein dysfunction contributes to hepatic steatosis and obesity in mice.. PLoS One. 2011;6(9):e23614..

Project PubMed

(2010). The key roles of elongases and desaturases in mammalian fatty acid metabolism: Insights from transgenic mice.. Prog Lipid Res. 2010 Apr;49(2):186-99..

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(2010). Effects of illicit dexamethasone upon hepatic drug metabolizing enzymes and related transcription factors mRNAs and their potential use as biomarkers in cattle.. J Agric Food Chem. 2010 Jan 27;58(2):1342-9..

Project PubMed

(2010). Impact of oral bisphenol A at reference doses on intestinal barrier function and sex differences after perinatal exposure in rats.. Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):448-53..

Project PubMed

(2009). Di-(2-ethylhexyl)-phthalate (DEHP) activates the constitutive androstane receptor (CAR): a novel signalling pathway sensitive to phthalates.. Biochem Pharmacol. 2009 Jun 1;77(11):1735-46..

Project Project PubMed

(2009). Identification of potential mechanisms of toxicity after di-(2-ethylhexyl)-phthalate (DEHP) adult exposure in the liver using a systems biology approach.. Toxicol Appl Pharmacol. 2009 May 1;236(3):282-92..

Project PubMed

(2009). Effects of dexamethasone, administered for growth promoting purposes, upon the hepatic cytochrome P450 3A expression in the veal calf.. Biochem Pharmacol. 2009 Feb 1;77(3):451-63..

Project PubMed

(2008). Cytochrome P450 inhibition profile in liver of veal calves administered a combination of 17beta-estradiol, clenbuterol, and dexamethasone for growth-promoting purposes.. Food Chem Toxicol. 2008 Aug;46(8):2849-55..

Project PubMed

(2008). High potency of bioactivation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in mouse colon epithelial cells with Apc(Min) mutation.. Mutat Res. 2008 May 31;653(1-2):34-43..

Project PubMed

(2008). Effect of breed upon cytochromes P450 and phase II enzyme expression in cattle liver.. Drug Metab Dispos. 2008 May;36(5):885-93..

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(2008). Chronic high-fat diet affects intestinal fat absorption and postprandial triglyceride levels in the mouse.. J Lipid Res. 2007 Feb;48(2):278-87..

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(2007). Fumonisin B1 exposure and its selective effect on porcine jejunal segment: sphingolipids, glycolipids and trans-epithelial passage disturbance.. Biochem Pharmacol. 2007 Jun 30;74(1):144-52..

Project PubMed