Changes in the expression of drug metabolizing enzymes in the brain by the brain disease and its therapeutic drugs

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08385
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Meijo University
• Principal Investigator: KATOH Miki 名城大学, 薬学部, 准教授 (70345594)
• Co-Investigator(Kenkyū-buntansha): 灘井 雅行 名城大学, 薬学部, 教授 (00295544)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 異物解毒機構 / 薬物代謝酵素 / 脳疾患 / てんかん / 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 several drug-metabolizing enzymes (DMEs) in the cortex and hippocampus, where epileptiform activity propagated and oxidative stress occurred. The changes in their expression varied among the enzymes. The oxidative stress and the alteration of cytosolic calcium concentration could be involved in the alteration. The interaction between nuclear receptors is also responsible for the DME expression. Moreover, anti-epileptic drugs also changed the DME expression in the brain. Therefore, we clarified that the DME expression in the brain regions would be changed by both brain disease and its therapeutic drugs.

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、高齢化に伴い、脳神経疾患の罹患率が増加している。脳神経疾患の一つであるてんかんは、主として薬物療法が行われるが、薬物抵抗性を示す難治性のものが増えている。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。てんかんの発症部位であり、かつ治療薬の作用部位である脳において、疾病と治療薬の両者が異物解毒機構を担う薬物代謝酵素に及ぼす影響を解明した本結果は、脳精神疾患の薬物治療を適正化するために、重要な情報を提供できたと考える。