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), CdCl2 (0.1 mmol/l), CuCl2 (0.03 mmol/l), Na3VO4 (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 Na3VO4 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 1-butanol in the liver. The MDA increase, however, was much higher after Na3VO4 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 Na3VO4 induced increase of MDA in liver and perfusate, the hepatic ATP and GSH level reductions induced by 1-butanol and attenuated the reduction of oxygen consumption induced by CuCl2 and t-BuOOH. Glycine, however, did not reverse the reductions of oxygen consumption induced by CdCl2 and Na3VO4, the suppressions of bile flow and, with the exception of 1-butanol, the decreases of hepatic ATP levels induced by all agents.
Institut für Toxikologie der Medizinischen Universität zu Lübeck, Germany.
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Deters
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Siegers
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Strubelt
D020001:1-Butanol / Q000633:toxicity; D000255:Adenosine Triphosphate / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000187:drug effects; D002104:Cadmium / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D003300:Copper / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D005998:Glycine / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D010545:Peroxides / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D014638:Vanadates / Q000633:toxicity; D020122:tert-Butylhydroperoxide
D010545:Peroxides; D002104:Cadmium; D014638:Vanadates; D008315:Malondialdehyde; D003300:Copper; D000255:Adenosine Triphosphate; D020001:1-Butanol; D020122:tert-Butylhydroperoxide; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase; D005978:Glutathione; D005998:Glycine