EXCLI J EXCLI Journal 1611-2156 Leibniz Research Centre for Working Environment and Human Factors 2017-1039 10.17179/excli2017-1039 Doc1330 Editorial material Highlight report: Monitoring cytochrome P450 activities in living hepatocytes Ghallab Ahmed * 1 Forensic Medicine and Toxicology Department, Faculty of Veterinary Medicine, South Valley University, Qena, Egypt *To whom correspondence should be addressed: Ahmed Ghallab, Forensic Medicine and Toxicology Department, Faculty of Veterinary Medicine, South Valley University, Qena, Egypt, E-mail: ghallab@vet.svu.edu.eg 22 12 2017 2017 16 1330 1331 11 12 2017 18 12 2017 Copyright © 2017 Ghallab 2017

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Recently, Jannick Theobald and Xinlai Cheng from Heidelberg University published a methods' paper how to monitor cytochrome P450 (CYP) activities in living hepatocytes (Theobald et al., 2017[15]). For this purpose, the authors used substrates that are metabolized by CYP enzymes thereby forming highly fluorescent leaving groups that were quantified by a plate reader. This technique allows repeated real-time measurements of cultivated hepatocytes over extincted time periods (Theobald et al., 2017[15]). The monitoring technique was validated by the use of CYP inducers and was applied to characterize differentiating HepaRG cells. The authors conclude that the fluorescence-based assay can easily be used as a tool to characterize hepatocyte in vitro systems.

Hepatotoxicity still represents a major challenge in drug development (Leist et al., 2017[8]; Schenk et al., 2017[12]; Reif et al., 2017[11]; Jansen et al., 2017[6]; Crespo Yanguas et al., 2016[3]; Stöber, 2015[13], 2016[14]; Yanguas et al., 2016[19]; Braeuning and Schwarz, 2016[2]).

Currently, much effort is invested to develop improved hepatocyte in vitro systems (Godoy et al., 2013[5]; Ramboer et al., 2015[10]; Verhulst et al., 2015[18]; Pfeiffer et al., 2015[9]; Kim et al., 2015[7]) and in silico techniques (Ghallab et al., 2016[4]; Bartl et al., 2015[1]; Vartak et al., 2016[17]; Thiel et al., 2015[16]). The technique presented by Theobald and colleagues can easily be integrated into in vitro systems and should therefore facilitate characterization of cultivated hepatocytes.

Bartl M Pfaff M Ghallab A Driesch D Henkel SG Hengstler JG Optimality in the zonation of ammonia detoxification in rodent liver Arch Toxicol 2015 89 2069 2078 Braeuning A Schwarz M Is the question of phenobarbital as potential liver cancer risk factor for humans really resolved? Arch Toxicol 2016 90 1525 1526 Crespo Yanguas S Willebrords J Maes M da Silva TC Veloso Alves Pereira I Cogliati B Connexins and pannexins in liver damage EXCLI J 2016 15 177 186 Ghallab A Cellière G Henkel SG Driesch D Hoehme S Hofmann U Model-guided identification of a therapeutic strategy to reduce hyperammonemia in liver diseases J Hepatol 2016 64 860–71 Godoy P Hewitt NJ Albrecht U Andersen ME Ansari N Bhattacharya S Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME Arch Toxicol 2013 87 1315 1530 Jansen PL Ghallab A Vartak N Reif R Schaap FG Hampe J The ascending pathophysiology of cholestatic liver disease Hepatology 2017 65 722 738 Kim JY Fluri DA Marchan R Boonen K Mohanty S Singh P 3D spherical microtissues and microfluidic technology for multi-tissue experiments and analysis J Biotechnol 2015 205 24 35 Leist M Ghallab A Graepel R Marchan R Hassan R Bennekou SH Adverse outcome pathways: opportunities, limitations and open questions Arch Toxicol 2017 91 3477 3505 Pfeiffer E Kegel V Zeilinger K Hengstler JG Nüssler AK Seehofer D Featured article: Isolation, characterization, and cultivation of human hepatocytes and non-parenchymal liver cells Exp Biol Med (Maywood) 2015 240 645 656 Ramboer E Rogiers V Vanhaecke T Vinken M Effects of Trichostatin A on drug uptake transporters in primary rat hepatocyte cultures EXCLI J 2015 14 567 576 Reif R Ghallab A Beattie L Günther G Kuepfer L Kaye PM In vivo imaging of systemic transport and elimination of xenobiotics and endogenous molecules in mice Arch Toxicol 2017 91 1335 1352 Schenk A Ghallab A Hofmann U Hassan R Schwarz M Schuppert A Physiologically-based modelling in mice suggests an aggravated loss of clearance capacity after toxic liver damage Sci Rep 2017 7 1 6224 Stöber R Drug-induced mitochondrial impairment in liver cells EXCLI J 2015 14 1297 1299 Stöber R Pathophysiology of cholestatic liver disease and its relevance for in vitro tests of hepatotoxicity EXCLI J 2016 15 870 871 Theobald J Cheng X Ghanem A Gaitantzi H Song G Klipp E Monitoring cytochrome P450 activity in living hepatocytes by chromogenic substrates in response to drug treatment or during cell maturation Arch Toxicol 5 12 2017 Epub ahead of print Thiel C Schneckener S Krauss M Ghallab A Hofmann U Kanacher T A systematic evaluation of the use of physiologically based pharmacokinetic modeling for cross-species extrapolation J Pharm Sci 2015 104 191 206 Vartak N Damle-Vartak A Richter B Dirsch O Dahmen U Hammad S Cholestasis-induced adaptive remodeling of interlobular bile ducts Hepatology 2016 63 951 964 Verhulst S Best J van Grunsven LA Dollé L Advances in hepatic stem/progenitor cell biology EXCLI J 2015 14 33 47 Yanguas SC Cogliati B Willebrords J Maes M Colle I van den Bossche B Experimental models of liver fibrosis Arch Toxicol 2016 90 1025 1048