Deters M, Strubelt O, Younes M
Institut für Toxikologie der Medizinischen Universität zu Lübeck, Germany.
Res Commun Mol Pathol Pharmacol. 1997 Aug;97(2):199-213.
Isolated perfused livers from rats fasted 16 h before surgery showed a strong decrease in oxygen consumption as well as hepatotoxic responses when subjected to 30 min of hypoxia (95%, N2/5% CO2) followed by 90 min of reoxygenation (95% O2/5% CO2). Toxicity was evident by a release of enzymes (LDH, GPT, GLDH) into the perfusate and by a nearly complete suppression of bile flow. Hepatic reduced gluthathione dropped to about 20% and hepatic ATP to about 50% of the initial values. Furthermore, the concentrations of thiobarbituric acid reactive (TBA) material increased eightfold in the perfusate and by 70% of the control values in the livers. Glycine added to the perfusate at concentrations of 3, 6 and 12 mmol/l prevented dose-dependently all measures of hepatotoxicity as well as the indices of lipid peroxidation induced by hypoxia/reoxygenation. A maximal and nearly complete protection was obtained with 12 mmol/l glycine. Glycine increased the bile flow of perfused livers not subjected to hypoxia and attenuated the drop of bile flow induced by hypoxia-reoxygenation. Ligation of the bile duct, however, did not influence the cytoprotective effects of glycine in hypoxia-reoxygenation induced hepatic injury. In conclusion, glycine is an effective antidote against hypoxia-regoxygenation induced injury of the isolated rat liver.
术前禁食16小时的大鼠的离体灌注肝脏，在经历30分钟缺氧（95%氮气/5%二氧化碳）随后90分钟复氧（95%氧气/5%二氧化碳）时，耗氧量显著下降，并出现肝毒性反应。毒性表现为酶（乳酸脱氢酶、谷丙转氨酶、谷氨酸脱氢酶）释放到灌注液中，以及胆汁分泌几乎完全受到抑制。肝脏中还原型谷胱甘肽降至初始值的约20%，肝ATP降至约50%。此外，灌注液中硫代巴比妥酸反应性（TBA）物质的浓度增加了八倍，肝脏中该物质浓度比对照值增加了70%。以3、6和12毫摩尔/升的浓度添加到灌注液中的甘氨酸，可剂量依赖性地预防缺氧/复氧诱导的所有肝毒性指标以及脂质过氧化指标。12毫摩尔/升的甘氨酸可提供最大且几乎完全的保护。甘氨酸增加了未经历缺氧的灌注肝脏的胆汁分泌，并减轻了缺氧-复氧诱导的胆汁分泌下降。然而，结扎胆管并不影响甘氨酸在缺氧-复氧诱导的肝损伤中的细胞保护作用
