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Effects of valproate, an HDAC inhibitor, on the expression of folate carriers and folate metabolism-related genes in the placenta of rats
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| Title: | Effects of valproate, an HDAC inhibitor, on the expression of folate carriers and folate metabolism-related genes in the placenta of rats |
| Authors: | Furugen, Ayako Browse this author →KAKEN DB | | Kanno, Yuki Browse this author | | Ohyama, Nanami Browse this author | | Kurosawa, Yuko Browse this author | | Jinno, Naoko Browse this author | | Narumi, Katsuya Browse this author →KAKEN DB | | Iseki, Ken Browse this author →KAKEN DB | | Kobayashi, Masaki Browse this author →KAKEN DB |
| Keywords: | Folate | | Transporter | | Enzyme | | Placenta | | Rat | | Valproate | | Histone deacetylase |
| Issue Date: | Oct-2021 |
| Publisher: | Japanese Society for the Study of Xenobiotics（日本薬物動態学会）JSSX |
| Journal Title: | Drug metabolism and pharmacokinetics |
| Volume: | 40 |
| Start Page: | 100409 |
| Publisher DOI: | 10.1016/j.dmpk.2021.100409 |
| Abstract: | 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 Folrfand 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. |
| Rights: | ©2021. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/87117 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 古堅 彩子
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