Modulation of cytochrome P450 2C9 by allyl isothiocyanate (AITC)

• Main Authors: Wei-Cheng Chen, 陳威程
• Other Authors: Yun-Ping Lim
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/24908833323082685417

碩士 === 中國醫藥大學 === 藥學系碩士班 === 102 === Drug - drug or drug - food interactions often lead to adverse drug reactions. Expression of drug-metabolizing enzymes (DMEs) is a common cause of adverse drug effects in some drugs. The liver is the largest organ in human, it contains multi-biological functions. Cytochrome P450 2C9 is predominantly regulated by nuclear receptors (NR), pregnane X receptor (PXR) and constitutive androstane receptor (CAR). Allyl isothiocyanate (AITC) is commonly found in cruciferous vegetables, with various biological activities, for example, anti-cancer and anti-bacterial. Until now, none of the report, study on the correlation between AITC with the cytochrome P450. In this study, we aimed to investigate the effect of AITC on the modulation of CYP2C9 through NRs. Using western blot and real time-PCR, we showed that AITC suppressed CYP2C9 protein and mRNA expression levels. AITC disrupted the coregulation effects of PXR/CAR with coactivation thus inhibited CYP2C9 reporter activities. By using DNA affinity precipitation assay, AITC inhibit nuclear receptors and related protein binding in CYP2C9 promoter. AITC will affect the CYP2C9 expression, the blood concentration of certain drugs may changed. Our results indicated that modification of CYP2C9 by consumption of AITC could have important implications on drug safety.