PROTECTION BY GLYCINE AGAINST HYPOXIA - REOXYGENATION INDUCED HEPATIC-INJURY

Isolated perfused livers from rats fasted 16 h before surgery showed a strong decrease in oxygen consumption as well as hepatotoxic response s when subjected to 30 min of hypoxia (95%, N-2/5% CO2) followed by 90 min of reoxygenation (95% O-2/5% CO2). Toxicity was evident by a rele ase of enzymes (LDH, GPT, GLDH) into the perfusate and by a nearly com plete suppression of bile flow. Hepatic reduced gluthathione dropped t o about 20% and hepatic ATP to about 50% of the initial values. Furthe rmore, the concentrations of thiobarbituric acid reactive (TBA) materi al increased eightfold in the perfusate and by 70% of the control valu es in the livers. Glycine added to the perfusate at concentrations of 3, 6 and 12 mmol/l prevented dose-dependently all measures of hepatoto xicity 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 li vers not subjected to hypoxia and attenuated the drop of bile flow ind uced by hypoxia-reoxygenation. Ligation of the bile duct, however, did not influence the cytoprotective effects of glycine in hypoxia-reoxyg enation induced hepatic injury. In conclusion, glycine is an effective antidote against hypoxia-regoxygenation induced injury of the isolate d rat liver.