Assessment of toxicity associated with protein degradation of drug-metabolizing enzymes by cehemicals in three-dimensional culture

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293029
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Environmental and hygienic pharmacy
• Research Institution: Hiroshima University
• Principal Investigator: Ohta Shigeru 広島大学, 大学院医歯薬保健学研究院(薬), 教授 (60160503)
• Co-Investigator(Kenkyū-buntansha): 佐能 正剛 広島大学, 医歯薬保健学研究院(薬), 助教 (00552267) ; 古武 弥一郎 広島大学, 医歯薬保健学研究院(薬), 准教授 (20335649)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 薬物代謝酵素 / ユビキチンプロテアソーム / アセトアミノフェン / 3次元培養

Outline of Final Research Achievements

There are few reports regarding toxicity and enzyme activity associated with drug-metabolizing enzyme accumulated by disruption of its protein degradation system. We have clarified that acetaminophen led to inhibit CYP3A protein degradation and accordingly induced its enzyme activity using 3-dimensional hepatocyte culture. The results could contribute formation of the reactive metabolite by CYP3A, which is known to induce hepatotoxicity. Acetaminophen analog also showed inhibitory effects on CYP3A degradation in 3-dimensional culture. These findings could lead to clarify the detailed mechanism.

Free Research Field

衛生薬学