PMID- 30744936
OWN - NLM
STAT- MEDLINE
DCOM- 20190725
LR  - 20190725
IS  - 1880-0920 (Electronic)
IS  - 1347-4367 (Linking)
VI  - 34
IP  - 2
DP  - 2019 Apr
TI  - Establishment of rat liver microsome-hydrogel system for in vitro phase II 
      metabolism and its application to study pharmacological effects of UGT 
      substrates.
PG  - 141-147
LID - S1347-4367(18)30457-9 [pii]
LID - 10.1016/j.dmpk.2019.01.005 [doi]
AB  - Studies on the efficacy evaluation of UDP-glucuronosyltransferases (UGTs) 
      substrates often ignore the existence of active metabolites. However, the present 
      study aims to establish an in-vitro Phase II metabolism system to predict their 
      pharmacological effects after metabolism. Rat liver microsomes (RLMs) 
      encapsulated in a F127'-Acr-Bis (FAB) hydrogel were placed in the incubation 
      system. Baicalein (BA) was chosen as a model drug and the metabolic activity was 
      investigated by quantitating the metabolite Baicalin (BG). The 3-(4, 
      5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was used to 
      measure the cell viability in Traditional cell culture system (TCCS) and 
      Microsome-hydrogel added to cell culture system for Phase II metabolism 
      (MHCCS-II). Finally, MHCCS-II was applied to predict the metabolic effects of 
      Oroxylin A (OA) and Wogonin (W). Compared to TCCS group, for HepG2 and 
      MCF-7 cells, BA in MHCCS-II led to lower survival ratios of cells (P < 0.05), 
      while for PC12 cells it led to higher survival ratios of cells (P < 0.01). For 
      HepG2 cells, OA and W showed obviously enhanced tumor inhibition after metabolism 
      with the IC(50) of 32.7 +/- 2.9 muM and 76.1 +/- 5.1 muM, respectively (P < 0.01). In 
      conclusion, the MHCCS-II could be a useful tool for studying the pharmacokinetics 
      and pharmacodynamics of UGTs substrates.
CI  - Copyright (c) 2019 The Japanese Society for the Study of Xenobiotics. Published by 
      Elsevier Ltd. All rights reserved.
FAU - Zhang, Zhe
AU  - Zhang Z
AD  - School of Pharmacy, Fudan University, Shanghai 201203, China.
FAU - Ma, Guo
AU  - Ma G
AD  - School of Pharmacy, Fudan University, Shanghai 201203, China.
FAU - Xue, Caifu
AU  - Xue C
AD  - School of Pharmacy, Fudan University, Shanghai 201203, China.
FAU - Sun, Hong
AU  - Sun H
AD  - School of Pharmacy, Fudan University, Shanghai 201203, China.
FAU - Wang, Ziteng
AU  - Wang Z
AD  - School of Pharmacy, Fudan University, Shanghai 201203, China.
FAU - Xiang, Xiaoqiang
AU  - Xiang X
AD  - School of Pharmacy, Fudan University, Shanghai 201203, China. Electronic address: 
      xiangxq@fudan.edu.cn.
FAU - Cai, Weimin
AU  - Cai W
AD  - School of Pharmacy, Fudan University, Shanghai 201203, China. Electronic address: 
      weimincai@fudan.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20190130
PL  - England
TA  - Drug Metab Pharmacokinet
JT  - Drug metabolism and pharmacokinetics
JID - 101164773
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Flavanones)
RN  - 0 (Flavonoids)
RN  - 0 (Hydrogels)
RN  - 49QAH60606 (baicalein)
RN  - 53K24Z586G (5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
RN  - POK93PO28W (wogonin)
MH  - Animals
MH  - Antineoplastic Agents/pharmacology
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Flavanones/*pharmacology
MH  - Flavonoids/pharmacology
MH  - Glucuronosyltransferase/*metabolism
MH  - Humans
MH  - Hydrogels/*metabolism
MH  - *Metabolic Detoxication, Phase II
MH  - Microsomes, Liver/*metabolism
MH  - Molecular Structure
MH  - Rats
MH  - Structure-Activity Relationship
MH  - Tumor Cells, Cultured
OTO - NOTNLM
OT  - Baicalein
OT  - FAB hydrogel
OT  - Liver microsome
OT  - Phase II metabolism
OT  - UGT
EDAT- 2019/02/13 06:00
MHDA- 2019/07/26 06:00
CRDT- 2019/02/13 06:00
PHST- 2018/11/01 00:00 [received]
PHST- 2019/01/21 00:00 [revised]
PHST- 2019/01/23 00:00 [accepted]
PHST- 2019/02/13 06:00 [pubmed]
PHST- 2019/07/26 06:00 [medline]
PHST- 2019/02/13 06:00 [entrez]
AID - S1347-4367(18)30457-9 [pii]
AID - 10.1016/j.dmpk.2019.01.005 [doi]
PST - ppublish
SO  - Drug Metab Pharmacokinet. 2019 Apr;34(2):141-147. doi: 
      10.1016/j.dmpk.2019.01.005. Epub 2019 Jan 30.