Hepatotoxicity of copper sulfide nanoparticles towards hepatocyte spheroids using a novel multi-concave agarose chip method

Aim: To explore the hepatotoxicity of copper sulfide nanoparticles (CuSNPs) toward hepatocyte spheroids. Materials & methods: Other than the traditional agarose method to generate hepatocyte spheroids, we developed a multi-concave agarose chip (MCAC) method to investigate changes in hepatocyte viability, morphology, mitochondrial membrane potential, reactive oxygen species and hepatobiliary transporter by CuSNPs. Results: The MCAC method allowed a large number of spheroids to be obtained per sample. CuSNPs showed hepatotoxicity in vitro through a decrease in spheroid viability, albumin/urea production and glycogen deposition. CuSNPs also introduced hepatocyte spheroid injury through alteration of mitochondrial membrane potential and reactive oxygen species, that could be reversed by N-acetyl-l-cysteine. CuSNPs significantly decreased the activity of BSEP transporter by downregulating its mRNA and protein levels. Activity of the MRP2 transporter remained unchanged. Conclusion: We observed the hepatotoxicity of CuSNPs in vitro with associated mechanisms in an advanced 3D culture system.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:16

Enthalten in:

Nanomedicine (London, England) - 16(2021), 17 vom: 06. Juli, Seite 1487-1504

Sprache:

Englisch

Beteiligte Personen:

Jiang, Tianyan [VerfasserIn]
Guo, Haoxiang [VerfasserIn]
Xia, Ya-Nan [VerfasserIn]
Liu, Yun [VerfasserIn]
Chen, Dandan [VerfasserIn]
Pang, Guibin [VerfasserIn]
Feng, Yahui [VerfasserIn]
Yu, Huan [VerfasserIn]
Wu, Yanxian [VerfasserIn]
Zhang, Shaodian [VerfasserIn]
Wang, Yangyun [VerfasserIn]
Wang, Yong [VerfasserIn]
Wen, Hairuo [VerfasserIn]
Zhang, Leshuai W [VerfasserIn]

Links:

Volltext

Themen:

789U1901C5
9012-36-6
Copper
Copper sulfide nanoparticles
Hepatobiliary transporters
Hepatotoxicity
Journal Article
Reactive oxygen species
Research Support, Non-U.S. Gov't
Sepharose
Spheroids
Sulfides

Anmerkungen:

Date Completed 04.08.2021

Date Revised 04.08.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.2217/nnm-2021-0011

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM327315458