High-throughput toxicity testing of chemicals and mixtures in organotypic multi-cellular cultures of primary human hepatic cells

Toxicology in Vitro : an International Journal Published in Association with BIBRA
Sophia M OrbachPadmavathy Rajagopalan

Abstract

High-throughput screening (HTS) of liver toxicants can bridge the gap in understanding adverse effects of chemicals on humans. Toxicity testing of mixtures is time consuming and expensive, since the number of possible combinations increases exponentially with the number of chemicals. The combination of organotypic culture models (OCMs) and HTS assays can lead to the rapidly evaluation of chemical toxicity in a cost and time-effective manner while prioritizing chemicals that warrant additional investigation. We describe the design, assembly and toxicant response of multi-cellular hepatic organotypic culture models comprised of primary human or rat cells assembled in 96-well plates (denoted as μOCMs). These models were assembled using automated procedures that did not affect hepatocyte function or viability, rendering them ideal for large-scale toxicity evaluations. Rat μOCMs were assembled to obtain insights into deviations from human toxicity. Four test chemicals (acetaminophen, ethanol, isoniazid, and perfluorooctanoic acid) were added to the μOCMs individually or in mixtures. HTS assays were utilized to measure cell death, apoptosis, glutathione depletion, mitochondrial membrane damage, and cytochrome P450 2E1 activity. The μ...Continue Reading

References

Jun 1, 1977·Journal of Pharmacokinetics and Biopharmaceutics·P K WilkinsonJ G Wagner
Aug 30, 1994·Biochemical and Biophysical Research Communications·J E SnawderD W Roberts
Apr 1, 1996·Alcoholism, Clinical and Experimental Research·T KoivistoC S Lieber
Mar 28, 1998·The Journal of Biological Chemistry·S B Mustafa, M S Olson
May 20, 1999·Annual Review of Pharmacology and Toxicology·F P Guengerich
Feb 24, 2001·Gastroenterology·W Z MehalI N Crispe
Oct 5, 2001·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·B N MelgertK Poelstra
Jan 29, 2002·Toxicological Sciences : an Official Journal of the Society of Toxicology·Hartmut JaeschkeJohn J Lemasters
Jun 14, 2002·Alcohol·Jan B Hoek, John G Pastorino
Jul 6, 2002·Forensic Science International : Synergy·Grzegorz TeresińskiRoman Madro
Jun 25, 2003·The Journal of Toxicological Sciences·Naomi Kudo, Yoichi Kawashima
Jun 19, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·M Teresa DonatoM José Gómez-Lechón
Jun 28, 2005·The Journal of Pharmacology and Experimental Therapeutics·Mohamed A AbdelmegeedRaymond F Novak
Oct 14, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Keerthi S GurugeNobuyoshi Yamashita
Nov 2, 2005·Tissue Engineering·Padmavathy RajagopalanMartin L Yarmush
Mar 1, 2006·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Christine P BiaginiStephan Chevalier
May 12, 2006·The Journal of Pharmacology and Experimental Therapeutics·B Alex MerrickKenneth B Tomer
Sep 12, 2006·Toxicological Sciences : an Official Journal of the Society of Toxicology·David J DixRobert J Kavlock
Dec 15, 2006·World Journal of Gastroenterology : WJG·George KoliosElias Kouroumalis
Dec 1, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Francesco PomatiEttore Zuccato
Dec 15, 2007·Free Radical Biology & Medicine·Yongke Lu, Arthur I Cederbaum
Dec 28, 2007·Proceedings of the National Academy of Sciences of the United States of America·Moo-Yeal LeeJonathan S Dordick
May 30, 2009·Environmental Health Perspectives·Richard JudsonEdwin Smith
Dec 19, 2009·Handbook of Experimental Pharmacology·Jack A HinsonLaura P James
Apr 7, 2010·Environmental Health Perspectives·Richard S JudsonDavid J Dix
Sep 10, 2010·Environmental Health Perspectives·David M ReifRobert J Kavlock
Oct 26, 2010·Biomaterials·Shufang ZhangHanry Yu
Nov 8, 2011·Assay and Drug Development Technologies·Timothy A MoellerMenghang Xia
Jan 19, 2012·Pharmacology & Therapeutics·Anna AstashkinaDavid W Grainger
Feb 2, 2013·Transplantation·Ashwani K SingalRussell H Wiesner
Apr 6, 2013·Tissue Engineering. Part C, Methods·Adam L LarkinPadmavathy Rajagopalan
Dec 18, 2013·Toxicology and Applied Pharmacology·Franck A AtienzarStéphane Dhalluin
Mar 13, 2014·Advanced Drug Delivery Reviews·Anna Astashkina, David W Grainger

❮ Previous
Next ❯

Citations

Aug 3, 2019·Annals of Biomedical Engineering·Lauren R Wills, Padmavathy Rajagopalan
Oct 14, 2018·Acta Biomaterialia·Sophia M OrbachPadmavathy Rajagopalan

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Antitubercular Agents (ASM)

Antitubercular agents are pharmacologic agents for treatment of tuberculosis. Discover the latest research on antitubercular agents here.

Antitubercular Agents

Antitubercular agents are pharmacologic agents for treatment of tuberculosis. Discover the latest research on antitubercular agents here.

Related Papers

Annals of Internal Medicine
T S MouldingG C Kanel
Toxicology in Vitro : an International Journal Published in Association with BIBRA
Sophia M OrbachPadmavathy Rajagopalan
© 2022 Meta ULC. All rights reserved