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Zebrafish larva as a reliable model for in vivo assessment of membrane remodeling involvement in the hepatotoxicity of chemical agents
Auteur(s) : Podechard, Normand Chevanne, Martine Fernier, Morgane Tête, Arnaud Collin, Aurore Cassio, Doris Kah, Olivier Lagadic-Gossmann, Dominique
Auteurs secondaires : Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) Signalisation calcique et interactions cellulaires dans le foie ; Université Paris-Sud - Paris 11 (UP11) - Institut National de la Santé et de la Recherche Médicale (INSERM) Supported by the Institut de Recherches scientifiques sur les Boissons (IREB) (contract numbers 2011/28, 2012/27, 2013/29), by the Agence Nationale de la Recherche (ANR) (STEATOX project; contract number ANR-13-CESA-0009) and also by European Union (FEDER), the Region Bretagne, the Conseil Général d'Ille-et-Vilaine, Rennes Métropole and the French Ministry of High Education and Research (MESR) for the financial support of the project Membratox (Contract number 32508, 350 keuros) and the project “Modernisation des équipements Rennes 2010–2013: Développement du plateau Membrane et Stress”(70 keuros). This study was also supported by the Structure Fédérative de Recherche en Biologie et Santé de Rennes (BIOSIT). Aurore Collin was a recipient of a fellowship from the Ligue Nationale contre le Cancer. ANR-13-CESA-0009, STEATOX, Impact des agents chimiques environnementaux sur les mécanismes de progression pathologique de la stéatose hépatique(2013)

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
The easy-to-use in vivo model, zebrafish larva, is being increasingly used to screen chemical-induced hepatotoxicity, with a good predictivity for various mechanisms of liver injury. However, nothing is known about its applicability in exploring the mechanism called membrane remodeling, depicted as changes in membrane fluidity or lipid raft properties. The aim of this study was, therefore, to substantiate the zebrafish larva as a suitable in vivo model in this context. Ethanol was chosen as a prototype toxicant because it is largely described, both in hepatocyte cultures and in rodents, as capable of inducing a membrane remodeling leading to hepatocyte death and liver injury. The zebrafish larva model was demonstrated to be fully relevant as membrane remodeling was maintained even after a 1-week exposure without any adaptation as usually reported in rodents and hepatocyte cultures. It was also proven to exhibit a high sensitivity as it discriminated various levels of cytotoxicity depending on the extent of changes in membrane remodeling. In this context, its sensitivity appeared higher than that of WIF-B9 hepatic cells, which is suited for analyzing this kind of hepatotoxicity. Finally, the protection afforded by a membrane stabilizer, ursodeoxycholic acid (UDCA), or by a lipid raft disrupter, pravastatin, definitely validated zebrafish larva as a reliable model to quickly assess membrane remodeling involvement in chemical-induced hepatotoxicity. In conclusion, this model, compatible with a high throughput screening, might be adapted to seek hepatotoxicants via membrane remodeling, and also drugs targeting membrane features to propose new preventive or therapeutic strategies in chemical-induced liver diseases.
ISSN: 0260-437X

hal-01526425
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526425
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526425/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526425/file/Zebrafish%20larva%20as%20a%20reliable%20model-Podechard%20JAT%202016%20revised.pdf
DOI : 10.1002/jat.3421

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