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

Logo poskytovatele
Logo poskytovatele

Varování

Publikace nespadá pod Ekonomicko-správní fakultu, ale pod Přírodovědeckou fakultu. Oficiální stránka publikace je na webu muni.cz.
Autoři

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

Rok publikování 2018
Druh Článek v odborném periodiku
Časopis / Zdroj ENVIRONMENTAL SCIENCE & TECHNOLOGY
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
www https://pubs.acs.org/doi/10.1021/acs.est.8b02291
Doi http://dx.doi.org/10.1021/acs.est.8b02291
Klíčová slova PRIMARY RAT HEPATOCYTES; HUMAN HEPATOMA-CELLS; MICROCYSTIN-LR; ALKALOID CYLINDROSPERMOPSIN; 1ST IDENTIFICATION; OXIDATIVE STRESS; SOUTHWEST CHINA; GENE-EXPRESSION; HL7702 CELLS; CYTOTOXICITY
Popis 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.
Související projekty:

Používáte starou verzi internetového prohlížeče. Doporučujeme aktualizovat Váš prohlížeč na nejnovější verzi.