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100 _a20220518a2021 k y0engy50 ba
101 0 _aeng
102 _aCH
135 _adrcn ---uucaa
181 0 _ai
182 0 _ab
200 1 _aToxicological Analysis of Hepatocytes Using FLIM Technique: In Vitro versus Ex Vivo Models
_fS. Rodimova, V. Elagin, M. Karabut [et al.]
203 _aText
_celectronic
300 _aTitle screen
320 _a[References: 85 tit.]
330 _aThe 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.
338 _bРоссийский научный фонд
_d19-15-00263
461 _tCells
463 _tVol. 10, iss. 11
_v[2894, 19 p.]
_d2021
610 1 _aэлектронный ресурс
610 1 _aтруды учёных ТПУ
610 1 _aFLIM
610 1 _amicrofluidic chip
610 1 _ahepatocyte
610 1 _aliver pathology
610 1 _ametabolism
610 1 _aчипы
610 1 _aгепатоциты
610 1 _aпаталогии
610 1 _aпечень
610 1 _aметаболизм
610 1 _aтоксикологический анализ
701 1 _aRodimova
_bS.
_gSvetlana
701 1 _aElagin
_bV.
_gVadim
701 1 _aKarabut
_bM.
_gMariya
701 1 _aKoryakina
_bI.
_gIrina
701 1 _aTimin
_bA. S.
_cChemist
_cAssociate Scientist of Tomsk Polytechnic University
_f1989-
_gAleksandr Sergeevich
_2stltpush
_3(RuTPU)RU\TPU\pers\37036
701 1 _aZagaynov
_bV.
_gVladimir
701 1 _aZyuzin
_bM. V.
_gMikhail
701 1 _aZagaynova
_bE. V.
_gElena Vladimirovna
701 1 _aKuznetsova
_bD.
_gDarjya
712 0 2 _aНациональный исследовательский Томский политехнический университет
_bИсследовательская школа химических и биомедицинских технологий
_c(2017- )
_h8120
_2stltpush
_3(RuTPU)RU\TPU\col\23537
801 2 _aRU
_b63413507
_c20220819
_gRCR
856 4 _uhttp://earchive.tpu.ru/handle/11683/72792
856 4 _uhttps://doi.org/10.3390/cells10112894
942 _cCF