Replacement Flame-Retardant 2-Ethylhexyldiphenyl Phosphate
(EHDPP) Disrupts Hepatic Lipidome: Evidence from Human 3D
Hepatospheroid Cell Culture

J 2023

Replacement Flame-Retardant 2-Ethylhexyldiphenyl Phosphate (EHDPP) Disrupts Hepatic Lipidome: Evidence from Human 3D Hepatospheroid Cell Culture

NEGI, Chander Kant; Darshak Chandulal GADARA; Jiří KOHOUTEK; Lola Murielle BAJARD ÉP.ESNER; Zdeněk SPÁČIL et al.

Základní údaje

Originální název

Replacement Flame-Retardant 2-Ethylhexyldiphenyl Phosphate (EHDPP) Disrupts Hepatic Lipidome: Evidence from Human 3D Hepatospheroid Cell Culture

Autoři

NEGI, Chander Kant; Darshak Chandulal GADARA; Jiří KOHOUTEK; Lola Murielle BAJARD ÉP.ESNER; Zdeněk SPÁČIL a Luděk BLÁHA

Vydání

ENVIRONMENTAL SCIENCE & TECHNOLOGY, WASHINGTON, AMER CHEMICAL SOC, 2023, 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: 10.900

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/23:00130485

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

3D spheroids; lipidomics; repeat dose toxicity; metabolic disrupting chemicals; flame retardants

Štítky

143180, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 8. 3. 2024 21:12, Mgr. Michaela Hylsová, Ph.D.

Anotace

V originále

The present study aims to evaluate the effects of repeated exposure to 2-ethylhexyldiphenyl phosphate (EHDPP) on human liver cells. In vitro threedimensional (3D) hepatospheroid cell culture was utilized to explore the potential mechanisms of EHDPP-mediated metabolic disruption through morphological, transcriptional, and biochemical assays. Lipidomics analysis was performed on the individual hepatospheroids to investigate the effects on intracellular lipid profiles, followed by hepatospheroid morphology, growth, functional parameters, and cytotoxicity evaluation. The possible mechanisms were delineated using the genelevel analysis by assessing the expression of key genes encoding for hepatic lipid metabolism. We revealed that exposure to EHDPP at 1 and 10 mu M for 7 days alters the lipid profile of human 3D hepatospheroids. Dysregulation in several lipid classes, including sterol lipids (cholesterol esters), sphingolipids (dihydroceramide, hexosylceramide, ceramide, sphingomyelin), glycerolipids (triglycerides), glycerophospholipids, and fatty acyls, was noted along with alteration in genes including ACAT1, ACAT2, CYP27A1, ABCA1, GPAT2, PNPLA2, PGC1 alpha, and Nrf2. Our study brings a novel insight into the metabolic disrupting effects of EHDPP and demonstrates the utility of hepatospheroids as an in vitro cell culture model complemented with omics technology (e.g., lipidomics) for mechanistic toxicity studies.

Návaznosti

EF15_003/0000469, projekt VaV

Název: Cetocoen Plus

EF17_043/0009632, projekt VaV

Název: CETOCOEN Excellence

857560, interní kód MU
(Kód CEP: EF17_043/0009632)

Název: CETOCOEN Excellence (Akronym: CETOCOEN Excellence)

Investor: Evropská unie, CETOCOEN Excellence, Spreading excellence and widening participation

859891, interní kód MU

Název: Best chemical risk assessment professionals for maximum Ecosystem Services benefit (Akronym: PRORISK)

Investor: Evropská unie, Best chemical risk assessment professionals for maximum Ecosystem Services benefit, MSCA Marie Skłodowska-Curie Actions (Excellent Science)

90121, velká výzkumná infrastruktura

Název: RECETOX RI

Přiložené soubory

2268997.pdf

Citovat

NEGI, Chander Kant; Darshak Chandulal GADARA; Jiří KOHOUTEK; Lola Murielle BAJARD ÉP.ESNER; Zdeněk SPÁČIL a Luděk BLÁHA. Replacement Flame-Retardant 2-Ethylhexyldiphenyl Phosphate (EHDPP) Disrupts Hepatic Lipidome: Evidence from Human 3D Hepatospheroid Cell Culture. ENVIRONMENTAL SCIENCE & TECHNOLOGY. WASHINGTON: AMER CHEMICAL SOC, 2023, roč. 57, č. 5, s. 2006-2018. ISSN 0013-936X. Dostupné z: https://doi.org/10.1021/acs.est.2c03998.

@article{2268997,
   author = {Negi, Chander Kant and Gadara, Darshak Chandulal and Kohoutek, Jiří and Bajard ép.Esner, Lola Murielle and Spáčil, Zdeněk and Bláha, Luděk},
   article_location = {WASHINGTON},
   article_number = {5},
   doi = {https://doi.org/10.1021/acs.est.2c03998},
   keywords = {3D spheroids; lipidomics; repeat dose toxicity; metabolic disrupting chemicals; flame retardants},
   language = {eng},
   issn = {0013-936X},
   journal = {ENVIRONMENTAL SCIENCE & TECHNOLOGY},
   title = {Replacement Flame-Retardant 2-Ethylhexyldiphenyl Phosphate (EHDPP) Disrupts Hepatic Lipidome: Evidence from Human 3D Hepatospheroid Cell Culture},
   url = {https://pubs.acs.org/doi/10.1021/acs.est.2c03998},
   volume = {57},
   year = {2023}
}

TY  - JOUR
ID  - 2268997
AU  - Negi, Chander Kant - Gadara, Darshak Chandulal - Kohoutek, Jiří - Bajard ép.Esner, Lola Murielle - Spáčil, Zdeněk - Bláha, Luděk
PY  - 2023
TI  - Replacement Flame-Retardant 2-Ethylhexyldiphenyl Phosphate (EHDPP) Disrupts Hepatic Lipidome: Evidence from Human 3D Hepatospheroid Cell Culture
JF  - ENVIRONMENTAL SCIENCE & TECHNOLOGY
VL  - 57
IS  - 5
SP  - 2006-2018
EP  - 2006-2018
PB  - AMER CHEMICAL SOC
SN  - 0013936X
KW  - 3D spheroids
KW  - lipidomics
KW  - repeat dose toxicity
KW  - metabolic disrupting chemicals
KW  - flame retardants
UR  - https://pubs.acs.org/doi/10.1021/acs.est.2c03998
N2  - The present study aims to evaluate the effects of repeated exposure to 2-ethylhexyldiphenyl phosphate (EHDPP) on human liver cells. In vitro threedimensional (3D) hepatospheroid cell culture was utilized to explore the potential mechanisms of EHDPP-mediated metabolic disruption through morphological, transcriptional, and biochemical assays. Lipidomics analysis was performed on the individual hepatospheroids to investigate the effects on intracellular lipid profiles, followed by hepatospheroid morphology, growth, functional parameters, and cytotoxicity evaluation. The possible mechanisms were delineated using the genelevel analysis by assessing the expression of key genes encoding for hepatic lipid metabolism. We revealed that exposure to EHDPP at 1 and 10 mu M for 7 days alters the lipid profile of human 3D hepatospheroids. Dysregulation in several lipid classes, including sterol lipids (cholesterol esters), sphingolipids (dihydroceramide, hexosylceramide, ceramide, sphingomyelin), glycerolipids (triglycerides), glycerophospholipids, and fatty acyls, was noted along with alteration in genes including ACAT1, ACAT2, CYP27A1, ABCA1, GPAT2, PNPLA2, PGC1 alpha, and Nrf2. Our study brings a novel insight into the metabolic disrupting effects of EHDPP and demonstrates the utility of hepatospheroids as an in vitro cell culture model complemented with omics technology (e.g., lipidomics) for mechanistic toxicity studies.
ER  -

NEGI, Chander Kant; Darshak Chandulal GADARA; Jiří KOHOUTEK; Lola Murielle BAJARD ÉP.ESNER; Zdeněk SPÁČIL a Luděk BLÁHA. Replacement Flame-Retardant 2-Ethylhexyldiphenyl Phosphate (EHDPP) Disrupts Hepatic Lipidome: Evidence from Human 3D Hepatospheroid Cell Culture. \textit{ENVIRONMENTAL SCIENCE \&{}amp; TECHNOLOGY}. WASHINGTON: AMER CHEMICAL SOC, 2023, roč.~57, č.~5, s.~2006-2018. ISSN~0013-936X. Dostupné z: https://doi.org/10.1021/acs.est.2c03998.

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