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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F18%3A00101601" target="_blank" >RIV/00216224:14310/18:00101601 - isvavai.cz</a>

Výsledek na webu

<a href="https://pubs.acs.org/doi/10.1021/acs.est.8b02291" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.est.8b02291</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.est.8b02291" target="_blank" >10.1021/acs.est.8b02291</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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 &gt; 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 (&gt;= 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 &lt;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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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 &gt; 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 (&gt;= 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 &lt;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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10511 - Environmental sciences (social aspects to be 5.7)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

ENVIRONMENTAL SCIENCE &amp; TECHNOLOGY

ISSN

0013-936X

e-ISSN

—

Svazek periodika

52

Číslo periodika v rámci svazku

17

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

10078-10088

Kód UT WoS článku

000444061100057

EID výsledku v databázi Scopus

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