Assessment of Hepatotoxic Potential of Cyanobacterial Toxins
Using 3D In Vitro Model of Adult Human Liver Stem Cells

J 2018

Assessment of Hepatotoxic Potential of Cyanobacterial Toxins Using 3D In Vitro Model of Adult Human Liver Stem Cells

BASU, Amrita; Aneta DYDOWICZOVÁ; Lucie ČTVERÁČKOVÁ; Libor JAŠA; James E. TROSKO et al.

Základní údaje

Originální název

Assessment of Hepatotoxic Potential of Cyanobacterial Toxins Using 3D In Vitro Model of Adult Human Liver Stem Cells

Autoři

BASU, Amrita; Aneta DYDOWICZOVÁ; Lucie ČTVERÁČKOVÁ; Libor JAŠA; James E. TROSKO; Luděk BLÁHA a Pavel BABICA

Vydání

ENVIRONMENTAL SCIENCE & TECHNOLOGY, WASHINGTON, AMER CHEMICAL SOC, 2018, 0013-936X

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10511 Environmental sciences

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 7.149

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/18:00101601

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

PRIMARY RAT HEPATOCYTES; HUMAN HEPATOMA-CELLS; MICROCYSTIN-LR; ALKALOID CYLINDROSPERMOPSIN; 1ST IDENTIFICATION; OXIDATIVE STRESS; SOUTHWEST CHINA; GENE-EXPRESSION; HL7702 CELLS; CYTOTOXICITY

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 18. 1. 2019 15:22, Mgr. Michaela Hylsová, Ph.D.

Anotace

V originále

Cyanotoxins microcystin-LR (MC-LR) and cylindrospermopsin (CYN) represent hazardous waterborne contaminants and potent human hepatotoxins. However, in vitro monolayer cultures of hepatic cell lines were found to recapitulate, poorly, major hepatocyte-specific functions and inadequately predict hepatotoxic effects of MC-LR and CYN. We utilized 3-dimensional (3D), scaffold-free spheroid cultures of human telomerase-immortalized adult liver stem cells HL1-hT1 to evaluate hepatotoxic potential of MC-LR and CYN. In monolayer cultures of HL1-hT1 cells, MC-LR did not induce cytotoxic effects (EC50 > 10 micromol/L), while CYN inhibited cell growth and viability (48h-96h EC50 approximate to 5.5-0.6 micromol/L). Growth and viability of small growing spheroids were inhibited by both cyanotoxins (>= 0.1 micromol/L) and were associated with blebbing and disintegration at the spheroid surface. Hepatospheroid damage and viability reduction were observed also in large mature spheroids, with viability 96h-EC50 values being 0.04 micromol/L for MC-LR and 0.1 micromol/L for CYN, and No Observed Effect Concentrations <0.01 micromol/L. Spheroid cultures of adult human liver stem cells HL1-hT1 exhibit sensitivity comparable to cultures of primary hepatocytes and provide a simple, practical, and cost-effective tool, which can be effectively used in environmental and toxicological research, including assessment of hepatotoxic potential and effect-based monitoring of various samples contaminated with toxic cyanobacteria.

Návaznosti

CZ.02.1.01/0.0/0.0/16_013/0001761, interní kód MU

Název: RECETOX RI - OP VVV (Akronym: RECETOX RI)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, RECETOX RI - OP VVV, PO 1 Posilování kapacit pro kvalitní výzkum

GA15-12408S, projekt VaV

Název: Role kmenových a diferencovaných jaterních buněk v hepatotoxicitě a hepatokarcinogenitě indukované cyanotoxiny

Investor: Grantová agentura ČR, Role kmenových a diferencovaných jaterních buněk v hepatotoxicitě a hepatokarcinogenitě indukované cyanotoxiny

LM2015051, projekt VaV

Název: Centrum pro výzkum toxických látek v prostředí (Akronym: RECETOX RI)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Výzkumná infrastruktura RECETOX

Citovat

BASU, Amrita; Aneta DYDOWICZOVÁ; Lucie ČTVERÁČKOVÁ; Libor JAŠA; James E. TROSKO; Luděk BLÁHA a Pavel BABICA. Assessment of Hepatotoxic Potential of Cyanobacterial Toxins Using 3D In Vitro Model of Adult Human Liver Stem Cells. ENVIRONMENTAL SCIENCE & TECHNOLOGY. WASHINGTON: AMER CHEMICAL SOC, 2018, roč. 52, č. 17, s. 10078-10088. ISSN 0013-936X. Dostupné z: https://doi.org/10.1021/acs.est.8b02291.

@article{1488086,
   author = {Basu, Amrita and Dydowiczová, Aneta and Čtveráčková, Lucie and Jaša, Libor and Trosko, James E. and Bláha, Luděk and Babica, Pavel},
   article_location = {WASHINGTON},
   article_number = {17},
   doi = {https://doi.org/10.1021/acs.est.8b02291},
   keywords = {PRIMARY RAT HEPATOCYTES; HUMAN HEPATOMA-CELLS; MICROCYSTIN-LR; ALKALOID CYLINDROSPERMOPSIN; 1ST IDENTIFICATION; OXIDATIVE STRESS; SOUTHWEST CHINA; GENE-EXPRESSION; HL7702 CELLS; CYTOTOXICITY},
   language = {eng},
   issn = {0013-936X},
   journal = {ENVIRONMENTAL SCIENCE & TECHNOLOGY},
   title = {Assessment of Hepatotoxic Potential of Cyanobacterial Toxins Using 3D In Vitro Model of Adult Human Liver Stem Cells},
   url = {https://pubs.acs.org/doi/10.1021/acs.est.8b02291},
   volume = {52},
   year = {2018}
}

TY  - JOUR
ID  - 1488086
AU  - Basu, Amrita - Dydowiczová, Aneta - Čtveráčková, Lucie - Jaša, Libor - Trosko, James E. - Bláha, Luděk - Babica, Pavel
PY  - 2018
TI  - Assessment of Hepatotoxic Potential of Cyanobacterial Toxins Using 3D In Vitro Model of Adult Human Liver Stem Cells
JF  - ENVIRONMENTAL SCIENCE & TECHNOLOGY
VL  - 52
IS  - 17
SP  - 10078-10088
EP  - 10078-10088
PB  - AMER CHEMICAL SOC
SN  - 0013936X
KW  - PRIMARY RAT HEPATOCYTES
KW  - HUMAN HEPATOMA-CELLS
KW  - MICROCYSTIN-LR
KW  - ALKALOID CYLINDROSPERMOPSIN
KW  - 1ST IDENTIFICATION
KW  - OXIDATIVE STRESS
KW  - SOUTHWEST CHINA
KW  - GENE-EXPRESSION
KW  - HL7702 CELLS
KW  - CYTOTOXICITY
UR  - https://pubs.acs.org/doi/10.1021/acs.est.8b02291
L2  - https://pubs.acs.org/doi/10.1021/acs.est.8b02291
N2  - Cyanotoxins microcystin-LR (MC-LR) and cylindrospermopsin (CYN) represent hazardous waterborne contaminants and potent human hepatotoxins. However, in vitro monolayer cultures of hepatic cell lines were found to recapitulate, poorly, major hepatocyte-specific functions and inadequately predict hepatotoxic effects of MC-LR and CYN. We utilized 3-dimensional (3D), scaffold-free spheroid cultures of human telomerase-immortalized adult liver stem cells HL1-hT1 to evaluate hepatotoxic potential of MC-LR and CYN. In monolayer cultures of HL1-hT1 cells, MC-LR did not induce cytotoxic effects (EC50 > 10 micromol/L), while CYN inhibited cell growth and viability (48h-96h EC50 approximate to 5.5-0.6 micromol/L). Growth and viability of small growing spheroids were inhibited by both cyanotoxins (>= 0.1 micromol/L) and were associated with blebbing and disintegration at the spheroid surface. Hepatospheroid damage and viability reduction were observed also in large mature spheroids, with viability 96h-EC50 values being 0.04 micromol/L for MC-LR and 0.1 micromol/L for CYN, and No Observed Effect Concentrations <0.01 micromol/L. Spheroid cultures of adult human liver stem cells HL1-hT1 exhibit sensitivity comparable to cultures of primary hepatocytes and provide a simple, practical, and cost-effective tool, which can be effectively used in environmental and toxicological research, including assessment of hepatotoxic potential and effect-based monitoring of various samples contaminated with toxic cyanobacteria.
ER  -

BASU, Amrita; Aneta DYDOWICZOVÁ; Lucie ČTVERÁČKOVÁ; Libor JAŠA; James E. TROSKO; Luděk BLÁHA a Pavel BABICA. Assessment of Hepatotoxic Potential of Cyanobacterial Toxins Using 3D In Vitro Model of Adult Human Liver Stem Cells. \textit{ENVIRONMENTAL SCIENCE \&{}amp; TECHNOLOGY}. WASHINGTON: AMER CHEMICAL SOC, 2018, roč.~52, č.~17, s.~10078-10088. ISSN~0013-936X. Dostupné z: https://doi.org/10.1021/acs.est.8b02291.

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