Use of primary cultures of rat hepatocytes to predict toxicity in the early development of new chemical entities

Toxicology in Vitro : an International Journal Published in Association with BIBRA
F PaillardJ A Vericat

Abstract

The new strategies for development of pharmacologically interesting compounds pose some limitations for standard toxicity assessment approaches due to: (1) increase in the number of compounds to be tested and (2) decrease in the amount of substance available for testing. In vitro methods are thus the only way to overcome such limitations. In this communication we present a cell-based model, using primary rat hepatocyte cultures, which we have validated using 23 compounds of the MEIC list as well as several Synthélabo proprietary products, covering a wide range of therapeutic indications. Our results show that our in vitro model gives a sufficient prediction for general toxicity by the oral route of administration (up to 2-4 weeks of treatment) in the rat to aid in decisions during early development. We also suggest that the comparative evaluation of the different parameters of cell toxicity examined may point to potential organ-related toxicity which could be further studied either with more complex in vitro or in vivo models. In conclusion, our results show that cell-based models for toxicity can be used for general screening purposes to predict in vivo toxicity in the early development of new chemical entities.

References

Apr 1, 1992·Cell Biology and Toxicology·R ShrivastavaR Massingham
Jun 1, 1986·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·R J RiddellM Balls
Jan 1, 1981·Toxicology·A P StammatiF Zucco
Feb 1, 1994·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·M C CallejaP Geladi
Dec 1, 1994·Toxicology in Vitro : an International Journal Published in Association with BIBRA·M J GarleJ R Fry
Jan 1, 1990·Toxicology in Vitro : an International Journal Published in Association with BIBRA·V Bianchi, E Fortunati

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Citations

Nov 26, 2008·Chemico-biological Interactions·Carlos R OliveiraClaudia Bincoletto
Mar 3, 2005·European Journal of Pharmacology·Daniel H A CorrêaMarcela Haun
May 8, 2004·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Mohamed AmeenQamar Rahman
Dec 25, 2010·Journal of Medicinal Food·Jaouad AnterAndrés Muñoz-Serrano
Nov 16, 2011·The Tohoku Journal of Experimental Medicine·Shinjiro TachibanaHidekuni Inadera
Dec 11, 2013·Environmental Toxicology and Pharmacology·Deepa K IngawaleSuresh R Naik
May 31, 2011·Mutation Research·Jaouad AnterMaría Dolores Luque de Castro
May 23, 2008·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·T S AbondanzaC Bincoletto
Dec 1, 2005·Life Sciences·Gardenia C G MilitãoLetícia V Costa-Lotufo
Mar 16, 2006·The Journal of Toxicological Sciences·Rie KikkawaIkuo Horii
Nov 24, 2004·Human & Experimental Toxicology·Patricia Silva MeloMarcela Haun
Aug 28, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Thiago A P de MoraesValdemiro A Silva Junior
Jul 2, 2009·Lab on a Chip·Yi-Chin TohHanry Yu
Jan 6, 2006·Environmental Health Perspectives·Johanna M BeekmanLaura Suter
Dec 18, 2013·Alternatives to Laboratory Animals : ATLA·Sandra HalwachsWalther Honscha
Mar 9, 2006·Alternatives to Laboratory Animals : ATLA·Sandra CoeckeAndrew Worth
Mar 26, 2021·Journal of Medicinal Chemistry·Jasleen K Sodhi, Leslie Z Benet
May 12, 2009·Toxicology Letters·Z H Liu, S Zeng

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