Toxicological Analysis of Hepatocytes Using FLIM Technique: In Vitro versus Ex Vivo Models

The search for new criteria indicating acute or chronic pathological processes resulting from exposure to toxic agents, testing of drugs for potential hepatotoxicity, and fundamental study of the mechanisms of hepatotoxicity at a molecular level still represents a challenging issue that requires the...

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Autores principales:	Svetlana Rodimova, Vadim Elagin, Maria Karabut, Irina Koryakina, Alexander Timin, Vladimir Zagainov, Mikhail Zyuzin, Elena Zagaynova, Daria Kuznetsova
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	FLIM microfluidic chip hepatocyte liver pathology metabolism Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/5c0e110288074fa3b6d2212568ab9cbd
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spelling	oai:doaj.org-article:5c0e110288074fa3b6d2212568ab9cbd2021-11-25T17:08:35ZToxicological Analysis of Hepatocytes Using FLIM Technique: In Vitro versus Ex Vivo Models10.3390/cells101128942073-4409https://doaj.org/article/5c0e110288074fa3b6d2212568ab9cbd2021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2894https://doaj.org/toc/2073-4409The search for new criteria indicating acute or chronic pathological processes resulting from exposure to toxic agents, testing of drugs for potential hepatotoxicity, and fundamental study of the mechanisms of hepatotoxicity at a molecular level still represents a challenging issue that requires the selection of adequate research models and tools. Microfluidic chips (MFCs) offer a promising in vitro model for express analysis and are easy to implement. However, to obtain comprehensive information, more complex models are needed. A fundamentally new label-free approach for studying liver pathology is fluorescence-lifetime imaging microscopy (FLIM). We obtained FLIM data on both the free and bound forms of NAD(P)H, which is associated with different metabolic pathways. In clinical cases, liver pathology resulting from overdoses is most often as a result of acetaminophen (APAP) or alcohol (ethanol). Therefore, we have studied and compared the metabolic state of hepatocytes in various experimental models of APAP and ethanol hepatotoxicity. We have determined the potential diagnostic criteria including the pathologically altered metabolism of the hepatocytes in the early stages of toxic damage, including pronounced changes in the contribution from the bound form of NAD(P)H. In contrast to the MFCs, the changes in the metabolic state of hepatocytes in the ex vivo models are, to a greater extent, associated with compensatory processes. Thus, MFCs in combination with FLIM can be applied as an effective tool set for the express modeling and diagnosis of hepatotoxicity in clinics.Svetlana RodimovaVadim ElaginMaria KarabutIrina KoryakinaAlexander TiminVladimir ZagainovMikhail ZyuzinElena ZagaynovaDaria KuznetsovaMDPI AGarticleFLIMmicrofluidic chiphepatocyteliver pathologymetabolismBiology (General)QH301-705.5ENCells, Vol 10, Iss 2894, p 2894 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	FLIM microfluidic chip hepatocyte liver pathology metabolism Biology (General) QH301-705.5
spellingShingle	FLIM microfluidic chip hepatocyte liver pathology metabolism Biology (General) QH301-705.5 Svetlana Rodimova Vadim Elagin Maria Karabut Irina Koryakina Alexander Timin Vladimir Zagainov Mikhail Zyuzin Elena Zagaynova Daria Kuznetsova Toxicological Analysis of Hepatocytes Using FLIM Technique: In Vitro versus Ex Vivo Models
description	The search for new criteria indicating acute or chronic pathological processes resulting from exposure to toxic agents, testing of drugs for potential hepatotoxicity, and fundamental study of the mechanisms of hepatotoxicity at a molecular level still represents a challenging issue that requires the selection of adequate research models and tools. Microfluidic chips (MFCs) offer a promising in vitro model for express analysis and are easy to implement. However, to obtain comprehensive information, more complex models are needed. A fundamentally new label-free approach for studying liver pathology is fluorescence-lifetime imaging microscopy (FLIM). We obtained FLIM data on both the free and bound forms of NAD(P)H, which is associated with different metabolic pathways. In clinical cases, liver pathology resulting from overdoses is most often as a result of acetaminophen (APAP) or alcohol (ethanol). Therefore, we have studied and compared the metabolic state of hepatocytes in various experimental models of APAP and ethanol hepatotoxicity. We have determined the potential diagnostic criteria including the pathologically altered metabolism of the hepatocytes in the early stages of toxic damage, including pronounced changes in the contribution from the bound form of NAD(P)H. In contrast to the MFCs, the changes in the metabolic state of hepatocytes in the ex vivo models are, to a greater extent, associated with compensatory processes. Thus, MFCs in combination with FLIM can be applied as an effective tool set for the express modeling and diagnosis of hepatotoxicity in clinics.
format	article
author	Svetlana Rodimova Vadim Elagin Maria Karabut Irina Koryakina Alexander Timin Vladimir Zagainov Mikhail Zyuzin Elena Zagaynova Daria Kuznetsova
author_facet	Svetlana Rodimova Vadim Elagin Maria Karabut Irina Koryakina Alexander Timin Vladimir Zagainov Mikhail Zyuzin Elena Zagaynova Daria Kuznetsova
author_sort	Svetlana Rodimova
title	Toxicological Analysis of Hepatocytes Using FLIM Technique: In Vitro versus Ex Vivo Models
title_short	Toxicological Analysis of Hepatocytes Using FLIM Technique: In Vitro versus Ex Vivo Models
title_full	Toxicological Analysis of Hepatocytes Using FLIM Technique: In Vitro versus Ex Vivo Models
title_fullStr	Toxicological Analysis of Hepatocytes Using FLIM Technique: In Vitro versus Ex Vivo Models
title_full_unstemmed	Toxicological Analysis of Hepatocytes Using FLIM Technique: In Vitro versus Ex Vivo Models
title_sort	toxicological analysis of hepatocytes using flim technique: in vitro versus ex vivo models
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5c0e110288074fa3b6d2212568ab9cbd
work_keys_str_mv	AT svetlanarodimova toxicologicalanalysisofhepatocytesusingflimtechniqueinvitroversusexvivomodels AT vadimelagin toxicologicalanalysisofhepatocytesusingflimtechniqueinvitroversusexvivomodels AT mariakarabut toxicologicalanalysisofhepatocytesusingflimtechniqueinvitroversusexvivomodels AT irinakoryakina toxicologicalanalysisofhepatocytesusingflimtechniqueinvitroversusexvivomodels AT alexandertimin toxicologicalanalysisofhepatocytesusingflimtechniqueinvitroversusexvivomodels AT vladimirzagainov toxicologicalanalysisofhepatocytesusingflimtechniqueinvitroversusexvivomodels AT mikhailzyuzin toxicologicalanalysisofhepatocytesusingflimtechniqueinvitroversusexvivomodels AT elenazagaynova toxicologicalanalysisofhepatocytesusingflimtechniqueinvitroversusexvivomodels AT dariakuznetsova toxicologicalanalysisofhepatocytesusingflimtechniqueinvitroversusexvivomodels
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Toxicological Analysis of Hepatocytes Using FLIM Technique: In Vitro versus Ex Vivo Models

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