Younes M, Strubelt O
Institut für Toxikologie der Medizinischen Universität zu Lübeck, FRG.
Res Commun Chem Pathol Pharmacol. 1988 Mar;59(3):369-81.
Isolated perfused livers from fasted, but not from fed rats showed hepatotoxic responses when subjected to 30 min of hypoxia followed by 60 min of reoxygenation. Toxicity was evident by a release of glutamate-pyruvate-transaminase, lactate dehydrogenase and glutathione into the perfusate, by a depletion of hepatic glutathione and by an accumulation of calcium in the liver. This indicates, that the liver is resistant to hypoxic injury as long as glycogen is present to maintain anaerobic ATP-synthesis. This is substantiated by the fact that addition of fructose--but not glucose--to the medium resulted in a protection of the liver against hypoxic injury concomitant with its degradation to lactate + pyruvate. Superoxide dismutase, catalase, desferrioxamine and allopurinol prevented hypoxic liver injury suggesting a substantial role of reactive oxygen species formed via the xanthine oxidase reaction in mediating hypoxic liver injury.
禁食大鼠而非进食大鼠的离体灌注肝脏，在经历30分钟缺氧后再进行60分钟复氧时会出现肝毒性反应。毒性表现为谷氨酸丙酮酸转氨酶、乳酸脱氢酶和谷胱甘肽释放到灌注液中，肝内谷胱甘肽耗竭以及肝脏中钙的积累。这表明，只要糖原存在以维持无氧ATP合成，肝脏就对缺氧损伤具有抗性。向培养基中添加果糖（而非葡萄糖）可保护肝脏免受缺氧损伤，并伴随其降解为乳酸 + 丙酮酸，这一事实证实了上述观点。超氧化物歧化酶、过氧化氢酶、去铁胺和别嘌呤醇可预防缺氧性肝损伤，提示通过黄嘌呤氧化酶反应形成的活性氧在介导缺氧性肝损伤中起重要作用。
