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ID 110385
タイトルヨミ
シンキ サイボウ エネルギー タイシャ スクリーニング ニ モトズイタ キュウセイ ジンショウガイ ヨボウヤク チリョウヤク ノ タンサク ト カイハツ
タイトル別表記
Nutrient‐sensitized screening for new drug development against Ischemic Kidney Injury
著者
岸, 誠司 徳島大学病院腎臓内科(検査部) KAKEN研究者をさがす
キーワード
AKI(Acute Kidney Injury)
Meclizine
Kennedy Pathway
資料タイプ
学術雑誌論文
抄録
Acute kidney injury(AKI)is a big clinical problem. In addition to high mortality rate, AKI is a potent risk factor of end-stage kidney disease. Ischemia reperfusion injury(IRI)is the leading cause of AKI and we have no specific treatment options to treat AKI. Shifting energy metabolism from mitochondrial respiration to glycolysis may offer a novel therapy against ischemic organ injury. Based on this theory, Meclizine, first-generation antihistamine used for motion sickness and vertigo, was identified in a novel chemical screen. Kidney tubular injury after ischemia reperfusion was significantly decreased in meclizine treated mice compared with the vehicle treated mice(100mg/kg of meclizine, 17 hours prior to ischemia). Meclizine treated kidney showed reduced inflammation, oxidative stress and mitochondrial fragmentation after IRI. Meclizine pretreatment reduced mitochondrial oxygen consumption. Reduced cell death and cytochrome c release was found in kidney tubular epithelial cells. Metabolic profiling revealed that Meclizine caused rapid accumulation of cellular phosphoethanolamine(PEtn). PEtn inhibits mitochondrial respiration and is an intermediate in phosphatidylethanolamine biosynthesis pathway(Kennedy pathway). In conclusion, Meclizine, or a derivative, is a candidate drug to minimize AKI risk and Kennedy pathway can be a novel therapeutic target for ischiemic kidney injury.
掲載誌名
四国医学雑誌
ISSN
00373699
cat書誌ID
AN00102041
出版者
徳島医学会
72
3-4
開始ページ
95
終了ページ
100
並び順
95
発行日
2016-08-25
EDB ID
フルテキストファイル
言語
jpn
著者版フラグ
出版社版
部局
病院
医学系