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Other studies suggested that HDAC inhibition might significantly activate the NF\u2010E2\u2010related factor\u20102 (Nrf2). Moreover, VPA activates mitogen\u2010activated protein kinases (MAPKs). MAPK pathways regulate Nrf2 transactivation domain activity. Uridine 5\u2032\u2010diphospho\u2010glucuronosyltransferase (UGT) 1A6 is one of the important isoforms to affect drug pharmacokinetics. UGT1A6 gene is regulated transcriptionally by AhR and Nrf2. The present study aimed to investigate whether UGT1A6 expression was changed by VPA and to elucidate the mechanism of the alteration. Following VPA treatment for 72\u00a0h in Caco\u20102 cells, UGT1A6 mRNA was increased by 7.9\u2010fold. Moreover, UGT1A6 mRNA was increased by other HDAC inhibitors, suggesting that HDAC inhibition caused the UGT1A6 mRNA induction. AhR and Nrf2 proteins in the nucleus of Caco\u20102 cells were increased by 1.5\u2010 and 1.7\u2010fold, respectively, following the VPA treatment. However, VPA treatment did not activate the extracellular signal\u2010regulated kinase (ERK) and c\u2010Jun N\u2010terminal kinase (JNK) pathways in Caco\u20102 cells. In conclusion, we observed that VPA induced UGT1A6 mRNA expression via AhR and Nrf2 pathways, but not via the ERK or JNK pathways.<\/jats:p>","DOI":"10.1002\/bdd.2328","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T06:20:05Z","timestamp":1661322005000},"page":"175-182","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Changes in uridine 5\u2032\u2010diphospho\u2010glucuronosyltransferase 1A6 expression by histone deacetylase inhibitor valproic acid"],"prefix":"10.1002","volume":"43","author":[{"given":"Yukiko","family":"Sakakibara","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy Meijo University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayaka","family":"Kojima","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Meijo University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Asai","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Meijo University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Nadai","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Meijo University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0825-6097","authenticated-orcid":false,"given":"Miki","family":"Katoh","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Meijo University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.5507\/bp.2012.038"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3109\/03602530903205492"},{"issue":"3","key":"e_1_2_8_4_1","first-page":"998","article-title":"Interindividual variability in acetaminophen glucuronidation by human liver microsomes: Identification of relevant acetaminophen UDP\u2010glucuronosyltransferase isoforms","volume":"299","author":"Court M. 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