Departament de Ciències Fisiològiques II, Universitat de Barcelona, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), 08907 Hospitalet de Llobregat (Catalunya), Spain.
Toxicol Lett. 2011 Feb 5;200(3):187-93. doi: 10.1016/j.toxlet.2010.11.014. Epub 2010 Nov 30.
IDPN (3,3'-iminodipropionitrile) causes a neurofilamentous proximal axonopathy. This study addressed the hypothesis that the butenenitriles (allylnitrile, cis-crotononitrile and trans-crotononitrile) have an IDPN-like axonopathic potential. First, male adult rats were exposed (i.p.) to IDPN, allylnitrile, cis-crotononitrile or trans-crotononitrile at 3.25 mmol/kg/day, 0.89 mmol/kg/day, 1.79 mmol/kg/day, or 3.75 mmol/kg/day for 3 consecutive days, respectively; lumbar dorsal root ganglia were examined for axonal swelling eight days after dosing. IDPN caused axonal swelling, a few swollen axons were recorded in one trans-crotononitrile animal, and no axonal abnormalities were observed following cis-crotononitrile or allylnitrile. To further evaluate trans-crotononitrile, additional rats were given this nitrile through a 10-day i.p. dosing schedule (2.5 mmol/kg/day, 2.75 mmol/kg/day, 3.0 mmol/kg/day or 3.25 mmol/kg/day) or a 9-week drinking water exposure (12.3, 24.6 and 49.1mM, three weeks each), and examined by light and electron microscopy. Semithin sections revealed no overt swelling in axons from several locations of the nervous system after trans-crotononitrile; quantitative analysis in the L5 dorsal root ganglion showed no increase in proximal axon diameter in comparison to control animals. At the transmission electron microscopy level, pathological effects were mild; they were mostly found in the animals submitted to the 10-day dosing regimen, and did not include evidence of significant axonal swelling. Although an axonopathic potential for the three unsaturated 4-carbon nitriles cannot be excluded, the present data indicated that this potential is significantly lower than that of IDPN.
IDPN（3,3'-亚氨基二丙腈）可导致神经原纤维性近侧轴索病。本研究旨在验证以下假设：丁烯腈（丙烯腈、顺-丁烯腈和反-丁烯腈）具有与 IDPN 类似的轴索病变潜能。首先，雄性成年大鼠分别经腹腔注射 IDPN、丙烯腈、顺-丁烯腈或反-丁烯腈，剂量为 3.25mmol/kg/天、0.89mmol/kg/天、1.79mmol/kg/天或 3.75mmol/kg/天，连续 3 天；8 天后，检测腰椎背根神经节的轴索肿胀情况。IDPN 导致轴索肿胀，在一只反-丁烯腈处理的动物中记录到少数肿胀的轴索，而顺-丁烯腈或丙烯腈处理后未见轴索异常。为了进一步评估反-丁烯腈，另外一些大鼠通过腹腔注射给药方案（2.5mmol/kg/天、2.75mmol/kg/天、3.0mmol/kg/天或 3.25mmol/kg/天）或在饮用水中暴露 9 周（12.3、24.6 和 49.1mM，每 3 周一次）给予该腈类化合物，并进行光镜和电镜检查。半薄切片显示，在神经系统的多个部位，反-丁烯腈处理后未见轴索明显肿胀；L5 背根神经节的定量分析显示，与对照组相比，近侧轴索直径无增加。在透射电镜水平，病理效应较轻；这些效应主要出现在接受 10 天给药方案的动物中，并且不包括明显轴索肿胀的证据。尽管不能排除这三种不饱和 4 碳腈具有轴索病变潜能，但本数据表明，其潜能明显低于 IDPN。
