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

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Publikace nespadá pod Pedagogickou fakultu, ale pod Přírodovědeckou fakultu. Oficiální stránka publikace je na webu muni.cz.
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NEGI Chander Kant GADARA Darshak Chandulal KOHOUTEK Jiří BAJARD ÉP.ESNER Lola Murielle SPÁČIL Zdeněk BLÁHA Luděk

Rok publikování 2023
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.2c03998
Doi http://dx.doi.org/10.1021/acs.est.2c03998
Klíčová slova 3D spheroids; lipidomics; repeat dose toxicity; metabolic disrupting chemicals; flame retardants
Přiložené soubory
Popis 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.
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