Changes in xenobiotic detoxification system by the brain disease and mental disorder

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07209
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Meijo University
• Principal Investigator: Katoh Miki 名城大学, 薬学部, 准教授 (70345594)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 異物解毒機構 / 薬物代謝酵素 / 脳精神疾患 / UDP-グルクロン酸転移酵素 / シトクロムP450 / 発現変動

Outline of Final Research Achievements

This study has shown that status epilepticus affects the expression of some drug metabolizing enzymes and drug transporters in the liver and small intestine, where epileptiform activity was not propagated. The changes in their expression varied among the enzymes. Furthermore, stress affected the expression of some drug metabolizing enzymes in the brain as well as in the liver and small intestine. However, there was no relationship concerning their alteration between tissues. Therefore, we clarified that the drug metabolizing enzymes and drug transporters in the brain, liver, and small intestine would be changed by both brain disease.

Free Research Field

薬物動態学

Academic Significance and Societal Importance of the Research Achievements

社会の高度化、複雑化に伴い、うつ病などの精神疾患や、てんかんのような神経活動の異常により引き起こされる脳疾患の罹患率が増加している。近年、第二の脳とも言われる腸と脳の機能的関連性が注目されている。薬物は一般的に生体内で異物解毒機構により解毒されて、薬理効果を失う。疾患による異物解毒機構の変動について、脳だけでなく、小腸、肝について明らかにしたことで、薬物の生体内での動態の変化を標的臓器だけでなく消失臓器を考慮して評価することが可能と考えられ、薬物治療の適正化のためにも貴重な情報を提供できたと考える。