In Vitro Testing of Basal Cytotoxicity: Establishment of an Adverse Outcome Pathway from Chemical Insult to Cell Death

Overview

Journal Toxicol In Vitro

Specialty Toxicology

Date 2016 Dec 13

PMID 27939612

Citations 31

Authors

Mathieu Vinken

Bas J Blaauboer

Affiliations

Soon will be listed here.

Abstract

In this paper, an in vitro basal cytotoxicity testing strategy is described for new chemical entities that lack any pre-existing information on potential toxicity. Special attention is paid to the selection of the cellular system, cytotoxicity assay and exposure conditions. This approach is based on a newly proposed generic adverse outcome pathway from chemical insult to cell death that consists of 3 steps, including initial cell injury, mitochondrial dysfunction and cell demise. The suggested strategy to consider in vitro basal cytotoxicity as a first step in evaluating the toxicity of new chemical entities can be placed in a tiered strategy that could be continued by evaluating more specific types of toxicity.

Citing Articles

An In Vitro Strategy to Evaluate Ketoprofen Phototoxicity at the Molecular and Cellular Levels.

Banach K, Kowalska J, Maszczyk M, Rzepka Z, Rok J, Wrzesniok D Int J Mol Sci. 2024; 25(23).

PMID: 39684359 PMC: 11641188. DOI: 10.3390/ijms252312647.

Development and in vitro evaluation of a lignin-PLGA nanocarrier for florfenicol delivery.

Trif E, Astete C, Libi S, Pall E, Tripon S, Coman C Vet Res Commun. 2024; 49(1):11.

PMID: 39556282 PMC: 11573854. DOI: 10.1007/s11259-024-10595-7.

Aggregatibacter is inversely associated with inflammatory mediators in sputa of patients with chronic airway diseases and reduces inflammation in vitro.

Goeteyn E, Taylor S, Dicker A, Bolle L, Wauters M, Joossens M Respir Res. 2024; 25(1):368.

PMID: 39395980 PMC: 11471032. DOI: 10.1186/s12931-024-02983-z.

Automated Image-Based Fluorescence Screening of Mitochondrial Membrane Potential in : An Advanced Ecotoxicological Testing Tool.

Abele C, Perez A, Hoglund A, Pierozan P, Breitholtz M, Karlsson O Environ Sci Technol. 2024; 58(36):15926-15937.

PMID: 39190186 PMC: 11393999. DOI: 10.1021/acs.est.4c02897.

Identification of neural-relevant toxcast high-throughput assay intended gene targets: Applicability to neurotoxicity and neurotoxicant putative molecular initiating events.

Mack C, Tsui-Bowen A, Smith A, Jensen K, Kodavanti P, Moser V Neurotoxicology. 2024; 103:256-265.

PMID: 38977203 PMC: 11895836. DOI: 10.1016/j.neuro.2024.07.001.

References

Yoon M, Blaauboer B, Clewell H . Quantitative in vitro to in vivo extrapolation (QIVIVE): An essential element for in vitro-based risk assessment. Toxicology. 2015; 332:1-3. DOI: 10.1016/j.tox.2015.02.002. View

Vanhaecke T, Henkens T, Kass G, Rogiers V . Effect of the histone deacetylase inhibitor trichostatin A on spontaneous apoptosis in various types of adult rat hepatocyte cultures. Biochem Pharmacol. 2004; 68(4):753-60. DOI: 10.1016/j.bcp.2004.05.022. View

Tuschl G, Hrach J, Walter Y, Hewitt P, Mueller S . Serum-free collagen sandwich cultures of adult rat hepatocytes maintain liver-like properties long term: a valuable model for in vitro toxicity and drug-drug interaction studies. Chem Biol Interact. 2009; 181(1):124-37. DOI: 10.1016/j.cbi.2009.05.015. View

Gennari A, Berghe C, Casati S, Castell J, Clemedson C, Coecke S . Strategies to replace in vivo acute systemic toxicity testing. The report and recommendations of ECVAM Workshop 50. Altern Lab Anim. 2005; 32(4):437-59. DOI: 10.1177/026119290403200417. View

Vinken M . The adverse outcome pathway concept: a pragmatic tool in toxicology. Toxicology. 2013; 312:158-65. DOI: 10.1016/j.tox.2013.08.011. View

Blaauboer B . Biokinetic modeling and in vitro-in vivo extrapolations. J Toxicol Environ Health B Crit Rev. 2010; 13(2-4):242-52. DOI: 10.1080/10937404.2010.483940. View

Grattagliano I, Bonfrate L, Diogo C, Wang H, Wang D, Portincasa P . Biochemical mechanisms in drug-induced liver injury: certainties and doubts. World J Gastroenterol. 2009; 15(39):4865-76. PMC: 2764962. DOI: 10.3748/wjg.15.4865. View

Seok J, Warren H, Cuenca A, Mindrinos M, Baker H, Xu W . Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci U S A. 2013; 110(9):3507-12. PMC: 3587220. DOI: 10.1073/pnas.1222878110. View

Groothuis F, Heringa M, Nicol B, Hermens J, Blaauboer B, Kramer N . Dose metric considerations in in vitro assays to improve quantitative in vitro-in vivo dose extrapolations. Toxicology. 2013; 332:30-40. DOI: 10.1016/j.tox.2013.08.012. View

10.

Malhi H, Gores G, Lemasters J . Apoptosis and necrosis in the liver: a tale of two deaths?. Hepatology. 2006; 43(2 Suppl 1):S31-44. DOI: 10.1002/hep.21062. View

11.

Schoonen W, Westerink W, Horbach G . High-throughput screening for analysis of in vitro toxicity. EXS. 2009; 99:401-52. DOI: 10.1007/978-3-7643-8336-7_14. View

12.

Vinken M . Adverse Outcome Pathways and Drug-Induced Liver Injury Testing. Chem Res Toxicol. 2015; 28(7):1391-7. PMC: 4596002. DOI: 10.1021/acs.chemrestox.5b00208. View

13.

Escher B, Eggen R, Schreiber U, Schreiber Z, Vye E, Wisner B . Baseline toxicity (narcosis) of organic chemicals determined by in vitro membrane potential measurements in energy-transducing membranes. Environ Sci Technol. 2002; 36(9):1971-9. DOI: 10.1021/es015844c. View

14.

Pessayre D, Fromenty B, Berson A, Robin M, Letteron P, Moreau R . Central role of mitochondria in drug-induced liver injury. Drug Metab Rev. 2011; 44(1):34-87. DOI: 10.3109/03602532.2011.604086. View

15.

Qiao L, Farrell G . The effects of cell density, attachment substratum and dexamethasone on spontaneous apoptosis of rat hepatocytes in primary culture. In Vitro Cell Dev Biol Anim. 1999; 35(7):417-24. DOI: 10.1007/s11626-999-0117-2. View

16.

Pessayre D, Mansouri A, Berson A, Fromenty B . Mitochondrial involvement in drug-induced liver injury. Handb Exp Pharmacol. 2009; (196):311-65. DOI: 10.1007/978-3-642-00663-0_11. View

17.

Kramer N, van Eijkeren J, Hermens J . Influence of albumin on sorption kinetics in solid-phase microextraction: consequences for chemical analyses and uptake processes. Anal Chem. 2007; 79(18):6941-8. DOI: 10.1021/ac070574n. View

18.

Fraczek J, Bolleyn J, Vanhaecke T, Rogiers V, Vinken M . Primary hepatocyte cultures for pharmaco-toxicological studies: at the busy crossroad of various anti-dedifferentiation strategies. Arch Toxicol. 2012; 87(4):577-610. DOI: 10.1007/s00204-012-0983-3. View

19.

Vinken M, Decrock E, Doktorova T, Ramboer E, De Vuyst E, Vanhaecke T . Characterization of spontaneous cell death in monolayer cultures of primary hepatocytes. Arch Toxicol. 2011; 85(12):1589-96. DOI: 10.1007/s00204-011-0703-4. View

20.

Kramer N, Di Consiglio E, Blaauboer B, Testai E . Biokinetics in repeated-dosing in vitro drug toxicity studies. Toxicol In Vitro. 2015; 30(1 Pt A):217-24. DOI: 10.1016/j.tiv.2015.09.005. View