2022 Fiscal Year Final Research Report

Control of uric acid by considering the change xanthine oxidase activity with the circadian rhythm

Research Project

PDF

Project/Area Number	19K07182
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	Hiroshima International University
Principal Investigator	Tayama Yoshitaka 広島国際大学, 薬学部, 准教授 (80389121)
Co-Investigator(Kenkyū-buntansha)	佐能正剛広島大学, 医系科学研究科(薬), 助教 (00552267) 杉原数美広島国際大学, 薬学部, 教授 (20271067) 岡村友理香広島国際大学, 健康科学部, 助教 (20645890) 太田茂広島大学, 医系科学研究科(薬), 名誉教授 (60160503)
Project Period (FY)	2019-04-01 – 2023-03-31
Keywords	キサンチンオキシドレダクターゼ / 日内変動
Outline of Final Research Achievements	Hyperuricemia is caused in part by the overproduction of uric acid. Xanthine, a precursor of uric acid, is oxidatively metabolized to uric acid by xanthine oxidoreductase (XOR). The purpose of this study is to provide guidance on how to reduce purine intake during times of high XOR activity. We observed the circadian rhythm XOR in the rat liver. The variation was high during the day and low at night. The activity difference was 1.4-fold. Further, the circadian rhythm of XOR activity in the liver was also associated with changes in protein expression. On the other hand, the XOR activity of the plasma fraction showed no circadian rhythm. Since the pharmacokinetics of drugs metabolized by XOR may reflect the circadian rhythm of XOR activity in the liver more than in the plasma, caution should be exercised when consuming a diet high in uric acid or administering drugs that are metabolized by XOR.
Free Research Field	臨床薬学
Academic Significance and Societal Importance of the Research Achievements	高尿酸血症の一因として、尿酸の過剰生産がある。尿酸の前駆物質であるxanthineは、xanthine oxidoreductase (XOR)にて尿酸へと酸化代謝される。今回、ラット肝を用いた検討であるが肝XORの日内変動を観察した。血漿XOR活性は肝に比して低値を示した。ヒトにおいても同様に日内変動が生じている可能性が高い。尿酸を多く含む食事の摂取やXORにて代謝される医薬品を投与する際には肝臓中XOR活性の日内変動を考慮することが重要である。XOR活性が高い時間帯にプリン体摂取を控えるなどの指導に役立てたい。