PMID- 34293696
OWN - NLM
STAT- MEDLINE
DCOM- 20220113
LR  - 20220113
IS  - 1880-0920 (Electronic)
IS  - 1347-4367 (Linking)
VI  - 40
DP  - 2021 Oct
TI  - Effects of valproate, an HDAC inhibitor, on the expression of folate carriers and 
      folate metabolism-related genes in the placenta of rats.
PG  - 100409
LID - S1347-4367(21)00030-6 [pii]
LID - 10.1016/j.dmpk.2021.100409 [doi]
AB  - Valproate (VPA), an antiepileptic drug, is known to inhibit histone deacetylases 
      (HDACs). Exposure to VPA during pregnancy increases several fetal risks. The 
      maintenance of folate level during pregnancy is essential for adequate fetal 
      development, and the placenta plays a critical role in supplying nutrients to the 
      fetus. The aim of this study was to elucidate the effects of VPA on the gene 
      expression of folate carriers and metabolizing enzymes in the rat placenta at 
      both mid and late gestation periods. Pregnant rats were orally administered VPA 
      on a single day or 4 days (repeated administration). Gene expression of folate 
      carriers (Folr1, Slc19a1, Slc46a1) and metabolizing enzymes (Cth, Mtr, Mtrr, 
      Mthfr, Dhfr) was assessed in the placenta on gestational day (GD) 13 or GD20. In 
      the control rats, the expression of Folr1, Slc46a1, Cth, and Mthfr tended to be 
      upregulated, whereas that of Mtrr and Dhfr was downregulated during gestation; 
      the expression of Slc19a1 and Mtr did not change. Repeated VPA administration 
      reduced the placental expression of Folr1and Mtr on GD20 and increased the 
      expression of Dhfr on GD13 compared with the control. These findings indicate 
      that administration of VPA alters the placental gene expression of folate 
      carriers and metabolism-related enzymes.
CI  - Copyright (c) 2021 The Japanese Society for the Study of Xenobiotics. Published by 
      Elsevier Ltd. All rights reserved.
FAU - Furugen, Ayako
AU  - Furugen A
AD  - Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, 
      Faculty of Pharmaceutical Sciences, Hokkaido University. Electronic address: 
      afurugen@pharm.hokudai.ac.jp.
FAU - Kanno, Yuki
AU  - Kanno Y
AD  - Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, 
      Faculty of Pharmaceutical Sciences, Hokkaido University.
FAU - Ohyama, Nanami
AU  - Ohyama N
AD  - Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, 
      Faculty of Pharmaceutical Sciences, Hokkaido University.
FAU - Kurosawa, Yuko
AU  - Kurosawa Y
AD  - Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, 
      Faculty of Pharmaceutical Sciences, Hokkaido University.
FAU - Jinno, Naoko
AU  - Jinno N
AD  - Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, 
      Faculty of Pharmaceutical Sciences, Hokkaido University.
FAU - Narumi, Katsuya
AU  - Narumi K
AD  - Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, 
      Faculty of Pharmaceutical Sciences, Hokkaido University.
FAU - Iseki, Ken
AU  - Iseki K
AD  - Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, 
      Faculty of Pharmaceutical Sciences, Hokkaido University.
FAU - Kobayashi, Masaki
AU  - Kobayashi M
AD  - Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, 
      Faculty of Pharmaceutical Sciences, Hokkaido University. Electronic address: 
      masaki@pharm.hokudai.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20210607
PL  - England
TA  - Drug Metab Pharmacokinet
JT  - Drug metabolism and pharmacokinetics
JID - 101164773
RN  - 0 (Anticonvulsants)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Minor Histocompatibility Antigens)
RN  - 0 (Proton-Coupled Folate Transporter)
RN  - 0 (Reduced Folate Carrier Protein)
RN  - 0 (Slc19a1 protein, rat)
RN  - 0 (Slc46a1 protein, rat)
RN  - 614OI1Z5WI (Valproic Acid)
RN  - 935E97BOY8 (Folic Acid)
SB  - IM
MH  - Animals
MH  - Anticonvulsants/therapeutic use
MH  - Female
MH  - Folic Acid
MH  - Histone Deacetylase Inhibitors/pharmacology
MH  - Membrane Transport Proteins
MH  - Minor Histocompatibility Antigens
MH  - *Placenta
MH  - Pregnancy
MH  - Proton-Coupled Folate Transporter/genetics
MH  - Rats
MH  - Reduced Folate Carrier Protein/genetics
MH  - *Valproic Acid
OTO - NOTNLM
OT  - Enzyme
OT  - Folate
OT  - Histone deacetylase
OT  - Placenta
OT  - Rat
OT  - Transporter
OT  - Valproate
COIS- Declaration of competing interest The authors declare no conflicts of interest.
EDAT- 2021/07/23 06:00
MHDA- 2022/01/14 06:00
CRDT- 2021/07/22 20:23
PHST- 2021/01/08 00:00 [received]
PHST- 2021/04/30 00:00 [revised]
PHST- 2021/05/31 00:00 [accepted]
PHST- 2021/07/23 06:00 [pubmed]
PHST- 2022/01/14 06:00 [medline]
PHST- 2021/07/22 20:23 [entrez]
AID - S1347-4367(21)00030-6 [pii]
AID - 10.1016/j.dmpk.2021.100409 [doi]
PST - ppublish
SO  - Drug Metab Pharmacokinet. 2021 Oct;40:100409. doi: 10.1016/j.dmpk.2021.100409. 
      Epub 2021 Jun 7.