Comparative Effects of Phosphoenolpyruvate, a Glycolytic Intermediate, as an Organ Preservation Agent with Glucose and N-Acetylcysteine against Organ Damage during Cold Storage of Mouse Liver and Kidney.

ISRN Pharmacology Pub Date : 2013-12-05 eCollection Date: 2013-01-01 DOI:10.1155/2013/375825
Yoichi Ishitsuka, Yusuke Fukumoto, Yuki Kondo, Mitsuru Irikura, Daisuke Kadowaki, Yuki Narita, Sumio Hirata, Hiroshi Moriuchi, Toru Maruyama, Naotaka Hamasaki, Tetsumi Irie
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引用次数: 4

Abstract

We evaluated the usefulness of phosphoenolpyruvate (PEP), a glycolytic intermediate with antioxidative and energy supplementation potentials, as an organ preservation agent. Using ex vivo mouse liver and kidney of a static cold storage model, we compared the effects of PEP against organ damage and oxidative stress during cold preservation with those of glucose or N-acetylcysteine (NAC). Lactate dehydrogenase (LDH) leakage, histological changes, and oxidative stress parameters (measured as thiobarbituric acid reactive substance and glutathione content) were determined. PEP (100 mM) significantly prevented an increase in LDH leakage, histological changes, such as tubulonecrosis and vacuolization, and changes in oxidative stress parameters during 72 h of cold preservation in mouse liver. Although glucose (100 mM) partly prevented LDH leakage and histological changes, no effects against oxidative stress were observed. By contrast, NAC inhibited oxidative stress in the liver and did not prevent LDH leakage or histological changes. PEP also significantly prevented kidney damage during cold preservation in a dose-dependent manner, and the protective effects were superior to those of glucose and NAC. We suggest that PEP, a functional carbohydrate with organ protective and antioxidative activities, may be useful as an organ preservation agent in clinical transplantation.

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糖酵解中间体磷酸烯醇丙酮酸与葡萄糖和n -乙酰半胱氨酸作为器官保鲜剂对小鼠肝脏和肾脏冷藏过程中器官损伤的比较研究。
我们评估了磷酸烯醇丙酮酸(PEP)作为器官保存剂的有效性,PEP是一种具有抗氧化和能量补充潜力的糖酵解中间体。以小鼠离体静态冷藏模型肝脏和肾脏为实验对象,比较了PEP与葡萄糖或n -乙酰半胱氨酸(NAC)在冷藏过程中对器官损伤和氧化应激的影响。测定乳酸脱氢酶(LDH)渗漏、组织学变化及氧化应激参数(以硫代巴比妥酸活性物质和谷胱甘肽含量测定)。PEP (100 mM)可显著抑制小鼠肝脏冷保存72 h期间LDH渗漏、小管坏死和空泡化等组织学变化以及氧化应激参数的变化。虽然葡萄糖(100 mM)部分阻止LDH泄漏和组织学改变,但没有观察到对氧化应激的影响。相反,NAC抑制肝脏氧化应激,但不能阻止LDH泄漏或组织学改变。PEP还能以剂量依赖性的方式显著预防冷藏过程中的肾损伤,其保护作用优于葡萄糖和NAC。PEP是一种具有器官保护和抗氧化活性的功能性碳水化合物,可作为器官保存剂应用于临床移植。
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