Pharmaco-metabonomic investigation of acetaminophen toxicity on rat primary hepatocytes in microfluidic biochips - Université Claude Bernard Lyon 1 Accéder directement au contenu
Communication Dans Un Congrès Année : 2013

Pharmaco-metabonomic investigation of acetaminophen toxicity on rat primary hepatocytes in microfluidic biochips

Résumé

Microfluidic bioartificial organs enable the spatial and temporal control of cell growth and biochemistry as well as the combination of organ-specific metabolic functions in endogenous and xenobiotic metabolism1. These properties are particularly relevant to testing the metabolic dose-response and building extrapolation models in both pharmaceutical and environmental toxicity screening. Thus, various microfluidic bioartificial organs have been proposed to reproduce human organs. Here we present a microfluidic bioartificial organ system combined with 1 H NMR-based metabolomic study to characterize an analgesic drug (N acetyl-para-aminophenol or APAP) toxicity. The objective of this systematic approach, based on innovative in vitro and in vivo methodologies to predict toxicity of substances, is to characterize culture media for biochip systems. This work is the continuity of a previous investigation carried out previously on hepatoma cell line2. APAP is a model molecule to validate in vitro biochips systems in toxicology approaches. We analyze using 1H high-field NMR (800 MHz) the metabolomic profiles of rat primary hepatocytes cultivated inside microfluidic systems (perfused dynamic system) with or without acetaminophen. Differences between controls and samples exposed to APAP were observed using supervised analysis. Acetaminophen met abolites such as its glucuronide conjuguate are identified on the corresponding metabolic fingerprint, as well as a range of amino-acids. A better differentiation between control and APAP is shown for long perfusion times (>24h). Results obtained on rat primary hepatocytes are also compared with in vivo study on rat biofluids.
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Dates et versions

hal-00980023 , version 1 (17-04-2014)

Identifiants

  • HAL Id : hal-00980023 , version 1

Citer

Claire Lopez, Mathilde Bayet-Robert, Marc-Emmanuel Dumas, Jean-Matthieu Prot, Alexandre R.R. Pery, et al.. Pharmaco-metabonomic investigation of acetaminophen toxicity on rat primary hepatocytes in microfluidic biochips. 7e Journées scientifiques du Réseau Français de Métabolomique et Fluxomique (RFMF), Jun 2013, Amiens, France. ⟨hal-00980023⟩
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