Evaluation of Three-Dimensional Cultured HepG2 Cells in a Nano Culture Plate System: an In Vitro Human Model of Acetaminophen Hepatotoxicity
Overdoses of acetaminophen (paracetamol, N-acetyl-p-aminophenol; APAP) cause severe liver injury, yet there is no common or high throughput in vitro human APAP model. This study examined the characteristics and usefulness of HepG2 cells grown in a nano culture plate (NCP) system, a three-dimensional...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Book |
| Published: |
Elsevier,
2014-01-01T00:00:00Z.
|
| Subjects: | |
| Online Access: | Connect to this object online. |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
MARC
| LEADER | 00000 am a22000003u 4500 | ||
|---|---|---|---|
| 001 | doaj_0773e84e64f64a6f8c4ac3993cb152d1 | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Kohei Aritomi |e author |
| 700 | 1 | 0 | |a Yoichi Ishitsuka |e author |
| 700 | 1 | 0 | |a Yoshiro Tomishima |e author |
| 700 | 1 | 0 | |a Daisuke Shimizu |e author |
| 700 | 1 | 0 | |a Nazuki Abe |e author |
| 700 | 1 | 0 | |a Tsuyoshi Shuto |e author |
| 700 | 1 | 0 | |a Mitsuru Irikura |e author |
| 700 | 1 | 0 | |a Hirofumi Kai |e author |
| 700 | 1 | 0 | |a Tetsumi Irie |e author |
| 245 | 0 | 0 | |a Evaluation of Three-Dimensional Cultured HepG2 Cells in a Nano Culture Plate System: an In Vitro Human Model of Acetaminophen Hepatotoxicity |
| 260 | |b Elsevier, |c 2014-01-01T00:00:00Z. | ||
| 500 | |a 1347-8613 | ||
| 500 | |a 10.1254/jphs.13135FP | ||
| 520 | |a Overdoses of acetaminophen (paracetamol, N-acetyl-p-aminophenol; APAP) cause severe liver injury, yet there is no common or high throughput in vitro human APAP model. This study examined the characteristics and usefulness of HepG2 cells grown in a nano culture plate (NCP) system, a three-dimensional culture method, as an in vitro human model for APAP-induced hepatotoxicity. The NCP-cultured HepG2 cells showed higher expression of mRNA and protein levels of cytochrome P450 2E1, which metabolizes APAP to a toxic metabolite, APAP-cysteine adduct formation, and higher sensitivity against APAP-induced cell injury compared with conventionally cultured cells. We demonstrated that treatment of APAP in NCP-cultured HepG2 cells shows key mechanistic features of APAP-induced hepatotoxicity, such as decreases in intracellular glutathione and mitochondrial membrane potential, activation of JNK, and cellular injury; and pharmacological agents, such as Cyclosporine A (a mitochondrial permeability transition inhibitor) and SP600125 (a JNK inhibitor), prevented cell injury induced by APAP exposure. In addition, the antidote of APAP-induced hepatotoxicity, N-acetylcysteine, could attenuate cellular injury induced by APAP in NCP-cultured HepG2 cells. We suggest that cellular injury induced by APAP treatment using an NCP-HepG2 system is a useful human model to study mechanisms and screen drug candidates of APAP-induced hepatotoxicity. [Supplementary Figures: available only at http://dx.doi.org/10.1254/jphs.13135FP] Keywords:: acetaminophen, liver injury, HepG2 cell, three-dimensional culture, human model | ||
| 546 | |a EN | ||
| 690 | |a Therapeutics. Pharmacology | ||
| 690 | |a RM1-950 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n Journal of Pharmacological Sciences, Vol 124, Iss 2, Pp 218-229 (2014) | |
| 787 | 0 | |n http://www.sciencedirect.com/science/article/pii/S1347861319302051 | |
| 787 | 0 | |n https://doaj.org/toc/1347-8613 | |
| 856 | 4 | 1 | |u https://doaj.org/article/0773e84e64f64a6f8c4ac3993cb152d1 |z Connect to this object online. |