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 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.
Deters
M
M
Institut für Toxikologie der Medizinischen Universität zu Lübeck, Germany.
Strubelt
O
O
Younes
M
M
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000378:metabolism; D001652:Bile Ducts / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D005998:Glycine / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010101:Oxygen Consumption; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances
D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase; D005978:Glutathione; D005998:Glycine