RRC ID 69183
著者 Kondo Y, Ishitsuka Y, Kadowaki D, Fukumoto Y, Miyamoto Y, Irikura M, Hirata S, Sato K, Maruyama T, Hamasaki N, Irie T.
タイトル Phosphoenolpyruvate, a glycolytic intermediate, as a cytoprotectant and antioxidant in ex-vivo cold-preserved mouse liver: a potential application for organ preservation.
ジャーナル J Pharm Pharmacol
Abstract OBJECTIVES:The aim of this study was to examine the effect of phosphoenolpyruvate (PEP), a glycolytic intermediate, on organ damage during cold preservation of liver.
METHODS:An ex-vivo mouse liver cold-preservation model and an in-vitro liver injury model induced by hydrogen peroxide in HepG2 cells were leveraged.
KEY FINDINGS:PEP attenuated the elevation of aminotransferases and lactate dehydrogenase leakage during organ preservation, histological changes and changes in oxidative stress parameters (measured as thiobarbituric acid reactive substance and glutathione content) induced by 72 h of cold preservation of the liver. The effects were comparable with the University of Wisconsin solution, a gold standard organ preservation agent. The decrease in ATP content in liver during the cold preservation was attenuated by PEP treatment. PEP prevented the cellular injury and increases in intracellular reactive oxygen species in HepG2 cells. In addition, PEP scavenged hydroxyl radicals, but had no effect on superoxide anion as evaluated by an electron paramagnetic resonance spin-trapping technique.
CONCLUSIONS:PEP significantly attenuated the injury, oxidative stress and ATP depletion in liver during cold preservation. The antioxidative potential of PEP was confirmed by in-vitro examination. We suggest that PEP acts as a glycolytic intermediate and antioxidant, and is particularly useful as an organ preservation agent in clinical transplantation.
巻・号 65(3)
ページ 390-401
公開日 2013-3-1
DOI 10.1111/j.2042-7158.2012.01602.x
PMID 23356848
MeSH Adenosine Triphosphate / metabolism Animals Antioxidants* Cell Line, Tumor Cryopreservation / methods* Cryoprotective Agents* Glycolysis Hep G2 Cells Humans Hydrogen Peroxide / metabolism L-Lactate Dehydrogenase / metabolism Liver* Male Mice Mice, Inbred C57BL Nitric Oxide Synthase Type II / metabolism Nitric Oxide Synthase Type III / metabolism Organ Preservation / methods* Oxidative Stress / physiology Phosphoenolpyruvate* Reactive Oxygen Species / metabolism Superoxides / metabolism Transaminases / metabolism
IF 2.571
リソース情報
ヒト・動物細胞 Hep G2(RCB1648)