Garrod Sarah, Bollard Mary E, Nicholls Andrew W, Connor Susan C, Connelly John, Nicholson Jeremy K, Holmes Elaine
Imperial College of Science, Technology and Medicine, Exhibition Road, London SW7 2AZ, United Kingdom.
Chem Res Toxicol. 2005 Feb;18(2):115-22. doi: 10.1021/tx0498915.
Hydrazine is a model toxin that induces both hepatotoxic and neurotoxic effects in experimental animals. The direct biochemical effects of hydrazine in kidney, liver, and brain tissue were assessed in male Sprague-Dawley rats using magic angle spinning nuclear magnetic resonance (NMR) spectroscopy. A single dose of hydrazine (90 mg/kg) resulted in changes to the biochemical composition of the liver after 24 h including an increase in triglycerides and beta-alanine, together with a decrease in hepatic glycogen, glucose, choline, taurine, and trimethylamine-N-oxide (TMAO). From histopathology measurements of liver tissue, minimal to mild hepatocyte alteration was observed in all animals at 24 h. The NMR spectra of the renal cortex at 24 h after dosing were dominated by a marked increase in the tissue concentration of 2-aminoadipate (2-AA) and beta-alanine, concomitant with depletions in TMAO, myo-inositol, choline, taurine, glutamate, and lysine. No alteration to the NMR spectral profile of the substantia nigra was observed after hydrazine administration, but perturbations to the relative concentrations of creatine, aspartate, myo-inositol, and N-acetyl aspartate were apparent in the hippocampus of hydrazine-treated animals at 24 h postdose. No overt signs of histopathological toxicity were observed in either the kidney or the brain regions examined. Elevated alanine levels were observed in all tissues indicative of a general inhibition of alanine transaminase activity. By 168 h postdose, NMR spectral profiles of treated rats appeared similar to those of matched controls for all tissue types indicative of recovery from toxic insult.
肼是一种典型毒素，可在实验动物中诱发肝毒性和神经毒性作用。使用魔角旋转核磁共振（NMR）光谱法，在雄性斯普拉格-道利大鼠中评估了肼在肾脏、肝脏和脑组织中的直接生化作用。单次给予肼（90 mg/kg）后24小时，肝脏的生化组成发生了变化，包括甘油三酯和β-丙氨酸增加，同时肝糖原、葡萄糖、胆碱、牛磺酸和氧化三甲胺（TMAO）减少。从肝脏组织的组织病理学测量来看，在24小时时所有动物均观察到最小至轻度的肝细胞改变。给药后24小时肾皮质的NMR光谱显示，2-氨基己二酸（2-AA）和β-丙氨酸的组织浓度显著增加，同时TMAO、肌醇、胆碱、牛磺酸、谷氨酸和赖氨酸减少。给予肼后，未观察到黑质的NMR光谱特征发生改变，但在给药后24小时，肼处理动物的海马体中肌酸、天冬氨酸、肌醇和N-乙酰天冬氨酸的相对浓度明显受到扰动。在所检查的肾脏或脑区域均未观察到明显的组织病理学毒性迹象。在所有组织中均观察到丙氨酸水平升高，表明丙氨酸转氨酶活性普遍受到抑制。给药后168小时，所有组织类型的处理大鼠的NMR光谱特征与匹配对照组相似，表明从毒性损伤中恢复。
