Phosphoenolpyruvate, a glycolytic intermediate, as a cytoprotectant and antioxidant in ex-vivo cold-preserved mouse liver: a potential application for organ preservation.
OBJECTIVE
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.


RESULTS
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.
Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
Yuki
Y
Kondo
Yoichi
Y
Ishitsuka
Daisuke
D
Kadowaki
Yusuke
Y
Fukumoto
Yohei
Y
Miyamoto
Mitsuru
M
Irikura
Sumio
S
Hirata
Keizo
K
Sato
Toru
T
Maruyama
Naotaka
N
Hamasaki
Tetsumi
T
Irie
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants; D045744:Cell Line, Tumor; D015925:Cryopreservation / Q000379:methods*; D003451:Cryoprotective Agents; D006019:Glycolysis; D056945:Hep G2 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009926:Organ Preservation / Q000379:methods*; D018384:Oxidative Stress / Q000502:physiology; D010728:Phosphoenolpyruvate; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D000637:Transaminases / Q000378:metabolism
D000975:Antioxidants; D003451:Cryoprotective Agents; D017382:Reactive Oxygen Species; D013481:Superoxides; D010728:Phosphoenolpyruvate; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D000637:Transaminases