In vitro assessment of mitochondrial toxicity to predict drug-induced liver injury
| Autor: | Bernard Fromenty, Pierre Rustin, Nelly Buron, Annie Borgne-Sanchez, Mathieu Porceddu |
|---|---|
| Přispěvatelé: | Mitologics S.A.S., Hôpital Robert Debré Paris, Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Drug Drug-induced liver injury media_common.quotation_subject [SDV]Life Sciences [q-bio] Pharmacology 03 medical and health sciences 0302 clinical medicine medicine Transmembrane potential media_common Liver injury Mitochondrial toxicity Chemistry Hepatotoxicity Respiratory chain medicine.disease In vitro 3. Good health Mitochondria 030104 developmental biology Liver Oxidative stress Hepatocytes DILI 030217 neurology & neurosurgery |
| Zdroj: | In vitro assessment of mitochondrial toxicity to predict drug-induced liver injury In vitro assessment of mitochondrial toxicity to predict drug-induced liver injury, Humana Press Inc., pp.283-300, 2018, Methods in Pharmacology and Toxicology, 978-1-4939-7677-5; 978-1-4939-7676-8. ⟨10.1007/978-1-4939-7677-5_14⟩ Methods in Pharmacology and Toxicology ISBN: 9781493976768 In vitro assessment of mitochondrial toxicity to predict drug-induced liver injury, 9781493976768, Humana Press Inc., pp.283-300, 2018, Methods in Pharmacology and Toxicology, 978-1-4939-7677-5; 978-1-4939-7676-8. ⟨10.1007/978-1-4939-7677-5_14⟩ |
| Popis: | International audience; Mitochondrial liability of drugs and other xenobiotics is a major issue for patients because such toxicity can damage different tissues and organs such as liver, heart, and muscle. Drug-induced mitochondrial toxicity is also a major concern for pharmaceutical industries. Indeed, it is now acknowledged that such mechanism of toxicity can induce severe, and sometimes fatal, liver injury which can lead to the interruption of clinical trials, or drug withdrawal after marketing, such as in the case of troglitazone. Therefore, drug-induced mitochondrial dysfunction is increasingly sought after by pharmaceutical companies by using reliable in vitro assays in order to discard potential mitochondrion-toxic drugs during drug discovery stage. This chapter presents the in vitro methods used to identify potential mitochondrion-toxic drugs. To this end, different types of biological materials are used such as isolated mouse liver mitochondria and the human hepatic HepaRG® cell line, which expresses the main enzymes and transcription factors involved in drug metabolism. The in vitro method we discussed allows to investigate several key mitochondrial parameters such as oxygen consumption, transmembrane potential, respiratory chain complex activities, and mtDNA levels. These investigations are able to detect not only direct and acute mitochondrial alterations due to parent drugs but also indirect and chronic mitochondrial liability that can be induced by secondary metabolites. Hence, it could be used to detect potential drug-induced mitochondrial liability and to understand the involved mechanisms. © 2018, Springer Science+Business Media, LLC, part of Springer Nature. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|