Ghatineh S, Morgan W, Preece N E, Timbrell J A
Department of Toxicology, London School of Pharmacy, UK.
Arch Toxicol. 1992;66(9):660-8. doi: 10.1007/BF01981506.
Using isolated rat hepatocytes the biochemical effects of hydrazine have been investigated using both conventional assay techniques and high resolution proton NMR. High resolution proton NMR revealed that hydrazine caused a significant increase in alanine and lactate levels in the incubation buffer, whereas levels of beta-hydroxybutyrate were decreased. NMR also detected metabolites of hydrazine notably acetylhydrazine and a cyclised hydrazone formed with alpha-ketoglutarate. Changes were detected in NADH and NADPH, ATP, succinate dehydrogenase (SDH) and total non-protein sulphydryl groups (TNPSH). However, the changes in pyridine nucleotides occurred at higher concentrations than those affecting succinate dehydrogenase and ATP. Similarly, the depletion of TNPSH occurred at a higher concentration and with a different time course to that seen with ATP depletion and inhibition of succinate dehydrogenase.
利用分离的大鼠肝细胞,采用传统检测技术和高分辨率质子核磁共振波谱法研究了肼的生化效应。高分辨率质子核磁共振波谱显示,肼使孵育缓冲液中的丙氨酸和乳酸水平显著升高,而β-羟基丁酸水平降低。核磁共振波谱还检测到了肼的代谢产物,尤其是乙酰肼以及与α-酮戊二酸形成的环化腙。检测到烟酰胺腺嘌呤二核苷酸(NADH)和烟酰胺腺嘌呤二核苷酸磷酸(NADPH)、三磷酸腺苷(ATP)、琥珀酸脱氢酶(SDH)以及总非蛋白巯基(TNPSH)发生了变化。然而,吡啶核苷酸的变化发生在比影响琥珀酸脱氢酶和ATP更高的浓度下。同样,TNPSH的消耗发生在比ATP消耗和琥珀酸脱氢酶抑制更高的浓度下,且时间进程不同。