Valproic acid (VPA) is well‐known as a histone deacetylase (HDAC) inhibitor. It has been reported that HDAC inhibitors enhance basal and aryl hydrocarbon receptor (AhR) ligand‐induced aryl hydrocarbon receptor‐responsive gene expression. Other studies suggested that HDAC inhibition might significantly activate the NF‐E2‐related factor‐2 (Nrf2). Moreover, VPA activates mitogen‐activated protein kinases (MAPKs). MAPK pathways regulate Nrf2 transactivation domain activity. Uridine 5′‐diphospho‐glucuronosyltransferase (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 h in Caco‐2 cells, UGT1A6 mRNA was increased by 7.9‐fold. 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‐2 cells were increased by 1.5‐ and 1.7‐fold, respectively, following the VPA treatment. However, VPA treatment did not activate the extracellular signal‐regulated kinase (ERK) and c‐Jun N‐terminal kinase (JNK) pathways in Caco‐2 cells. In conclusion, we observed that VPA induced UGT1A6 mRNA expression via AhR and Nrf2 pathways, but not via the ERK or JNK pathways.
Flavor improvement of boiledˆsh by addition of fermented rice bran,``Nukamiso'', and raw rice bran was investigated. Jack mackerelˆllet was boiled with lactic acid fermented rice bran or raw bran. Change of ‰avor during storage at 4°C was monitored using a gas chromatography-mass spectrometer, an electronic nose and a sensory test. Addition of fermented or raw rice bran prevented the generation of trimethylamine during boiling and the
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