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Expertise in hepatotoxicity induced by xenobiotics including ethanol and drugs, in particular in the context of obesity and nonalcoholic fatty liver disease (NAFLD).

Research topics and scientific objectives

The main objectives of my research is to determine the mechanisms of hepatotoxity induced by different xenobiotics including ethanol and drugs such as amiodarone and acetaminophen (APAP). The role of mitochondrial dysfunction and oxidative stress is more specifically studied.

In addition, my investigations try to decipher the mechanisms whereby some xenobiotics such ethanol and APAP are more toxic in the context of obesity and nonalcoholic fatty liver disease (NAFLD). The cytochrome P450 2E1 (CYP2E1) is particularly investigated in these studies since the activity of this enzyme is enhanced during NAFLD, thus increasing the generation of toxic reactive metabolites.

Education and main positions held

1990: Doctorate in Pharmacy (University of Paris 5).
1991: PhD in Pharmacology (University of Paris 6).
1999: Accreditation to Supervise Research (HDR-University of Paris 7).

1996: Recruited by INSERM as Research Assistant (CR1).
2006: Promoted to the rank of Director of Research (DR2).

Team leadership:
2006-2009: Leader of Team n°5 (Mitochondria and liver), INSERM Unit 773 (Centre de Recherche Biomédicale Bichat-Beaujon-CRB3 - Paris; Head: Marc Laburthe).
2010-2016: Leader of Team n°3 (Hepatotoxicity of xenobiotics: mechanisms and modulation by obesity), INSERM Unit 991 (Liver, Metabolisms and Cancer- Rennes; Head: Bruno Clément).

Current projects

Several projects pertaining to the toxic effects of different xenobiotics (drugs, ethanol and environmental contaminants) in normal and steatotic HepaRG cells and/or in lean and obese mice.

Selected publications

Acetaminophen-induced liver injury in obesity and nonalcoholic fatty liver disease.
Michaut A, Moreau C, Robin MA, Fromenty B.
Liver Int. 2014 Aug;34(7):e171-9.

Chronic exposure to low doses of pharmaceuticals disturbs the hepatic expression of circadian genes in lean and obese mice.
Anthérieu S, Le Guillou D, Coulouarn C, Begriche K, Trak-Smayra V, Martinais S, Porceddu M, Robin MA, Fromenty B.
Toxicol Appl Pharmacol. 2014 Apr 1;276(1):63-72.

Pentoxifylline aggravates fatty liver in obese and diabetic ob/ob mice by increasing intestinal glucose absorption and activating hepatic lipogenesis.
Massart J, Robin MA, Noury F, Fautrel A, Lettéron P, Bado A, Eliat PA, Fromenty B..
Br J Pharmacol. 2012 Mar;165(5):1361-74. .

Differences in early acetaminophen hepatotoxicity between obese ob/ob and db/db mice.
Aubert J, Begriche K, Delannoy M, Morel I, Pajaud J, Ribault C, Lepage S, McGill MR, Lucas-Clerc C, Turlin B, Robin MA, Jaeschke H, Fromenty B.
J Pharmacol Exp Ther. 2012 Sep;342(3):676-87.

Drug-induced toxicity on mitochondria and lipid metabolism: mechanistic diversity and deleterious consequences for the liver.
Begriche K, Massart J, Robin MA, Borgne-Sanchez A, Fromenty B.
J Hepatol. 2011 Apr;54(4):773-94.

HAL Publications

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