ID 110385
Title Transcription
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
Title Alternative
Nutrient‐sensitized screening for new drug development against Ischemic Kidney Injury
Author
Kishi, Seiji Department of Nephrology, Tokushima University Hospital KAKEN Search Researchers
Keywords
AKI(Acute Kidney Injury)
Meclizine
Kennedy Pathway
Content Type
Journal Article
Description
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.
Journal Title
四国医学雑誌
ISSN
00373699
NCID
AN00102041
Publisher
徳島医学会
Volume
72
Issue
3-4
Start Page
95
End Page
100
Sort Key
95
Published Date
2016-08-25
EDB ID
FullText File
language
jpn
TextVersion
Publisher
departments
University Hospital
Medical Sciences