Influence of glycine on the damage induced in isolated perfused rat liver by five hepatotoxic agents

Livers of fasted rats were perfused over 120 min in a recirculating hemoglobin-free system. Hepatotoxic injury induced by the addition of 1-butanol(130.2 mmol/l), CdCl(2) (0.1 mmol/l), CuCl(2) (0.03 mmol/l), Na(3)VO(4) (2 mmol/l) or t-butylhydroperoxide (t-BuOOH, 0.5 mmol/l) to the perfusate was shown by strong increases in lactate dehydrogenase (LDH) and glutamate-pyruvate transaminase (GPT) release, decreased oxygen consumption between 50 and 60%, and a nearly complete suppression of bile flow. Hepatic adenosine triphosphate (ATP) and reduced glutathione (GSH) concentrations were reduced by between 30 and 80%, and 20 and 80%, respectively. Only Na(3)VO(4) and t-BuOOH evoked increased releases of glutamate dehydrogenase (GLDH) in the perfusate. Malondialdehyde (MDA) concentrations were enhanced by all toxicants in the perfusate and by all except l-butanol in the liver. The MDA increase, however, was much higher after Na(3)VO(4) and t-BuOOH than after the other toxicants. When glycine (12 mmol/l) was added 30 min before the toxicants to the perfusate it prevented the enzyme releases induced by all hepatotoxic agents by about 80%. Furthermore, glycine prevented the Na(3)VO(4) induced increase of MDA in liver and perfusate, the hepatic ATP and GSH level reductions induced by l-butanol and attenuated the reduction of oxygen consumption induced by CuCl(2) and t-BuOOH. Glycine, however, did not reverse the reductions of oxygen consumption induced by CdCl(2) and Na(3)VO(4), the suppressions of bile flow and, with the exception of 1-butanol, the decreases of hepatic ATP levels induced by all agents. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.