Comparative analysis of bilirubin glucuronidation activity in canine and human primary hepatocytes using a 3D culture system

被引：1

作者：

Omori, Hisayoshi ^{[1
,2
]}

Chikamoto, Junko ^{[2
]}

Hirano, Takayuki ^{[2
]}

Besshi, Kazuhiko ^{[3
]}

Yoshimura, Naoaki ^{[1
]}

Hirata, Maki ^{[1
,4
]}

Otoi, Takeshige ^{[1
,4
]}

机构：

[1] Tokushima Univ, Bioinnovat Res Ctr, Tokushima, Tokushima, Japan

[2] Taiho Pharmaceut Co Ltd, Preclin Basic Res, Tokushima, Tokushima, Japan

[3] Taiho Pharmaceut Co Ltd, Discovery & Preclin Res Div, Tokushima, Tokushima, Japan

[4] Tokushima Univ, Fac Biosci & Bioind, Tokushima, Tokushima, Japan

来源：

IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL | 2022年 / 58卷 / 08期

关键词：

Bilirubin glucuronidation; Dog; Human; Primary hepatocyte; Spheroid; RECOMBINANT UGT1A1 ENZYME; UDP-GLUCURONOSYLTRANSFERASE; INCUBATION SYSTEMS; LIVER-MICROSOMES; CELLS; HEPG2; METABOLISM; EXPRESSION; SPHEROIDS; INDUCTION;

D O I：

10.1007/s11626-022-00711-9

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Species differences in bilirubin glucuronidation activity are observed between humans and dogs through liver microsomes and recombinant UDP-glucuronosyltransferase 1A1. Humans exhibit higher activity than that of dogs. In this study, bilirubin glucuronidation activity was examined in canine and human primary hepatocyte spheroids formed using a 3D culture system. When spheroid development in canine and human primary hepatocytes was evaluated on days 7 and 14 after the start of culture, canine primary hepatocyte spheroids had a more distinct spherical shape than human hepatocyte spheroids, irrespective of the culture period. Furthermore, mono- and di-glucuronide generation detected in spheroids were significantly higher (P < 0.05) in human primary hepatocytes than in canine primary hepatocytes after 24 h of incubation with bilirubin for each culture period. These results suggest that there are species differences in the bilirubin glucuronidation activity of primary hepatocytes with spheroid formation between humans and dogs, with the activity being higher in humans than in dogs.

引用

页码：712 / 718

页数：7

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