Deters M, Siegers C P, Strubelt O
Institut für Toxikologie der Medizinischen Universität zu Lübeck, Germany.
Toxicology. 1998 Jun 26;128(1):63-72. doi: 10.1016/s0300-483x(98)00048-1.
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.
在无血红蛋白的循环系统中，对禁食大鼠的肝脏进行120分钟的灌注。向灌注液中添加1 - 丁醇（130.2 mmol/l）、氯化镉（0.1 mmol/l）、氯化铜（0.03 mmol/l）、偏钒酸钠（2 mmol/l）或叔丁基过氧化氢（t - BuOOH，0.5 mmol/l）所诱导的肝毒性损伤表现为乳酸脱氢酶（LDH）和谷丙转氨酶（GPT）释放显著增加、耗氧量降低50%至60%以及胆汁分泌几乎完全受到抑制。肝三磷酸腺苷（ATP）和还原型谷胱甘肽（GSH）浓度分别降低了30%至80%和20%至80%。只有偏钒酸钠和叔丁基过氧化氢能使灌注液中谷氨酸脱氢酶（GLDH）的释放增加。所有毒物都会使灌注液中的丙二醛（MDA）浓度升高，除1 - 丁醇外，所有毒物都会使肝脏中的MDA浓度升高。然而，偏钒酸钠和叔丁基过氧化氢作用后MDA的增加幅度远高于其他毒物。当在毒物加入前30分钟向灌注液中添加甘氨酸（12 mmol/l）时，它能使所有肝毒性剂诱导的酶释放减少约80%。此外，甘氨酸可防止偏钒酸钠诱导的肝脏和灌注液中MDA增加、1 - 丁醇诱导的肝脏ATP和GSH水平降低，并减轻氯化铜和叔丁基过氧化氢诱导的耗氧量降低。然而，甘氨酸并不能逆转氯化镉和偏钒酸钠诱导的耗氧量降低以及胆汁分泌的抑制，除1 - 丁醇外，也不能逆转所有药剂诱导的肝脏ATP水平降低。
