Llorens J, Rodríguez-Farré E
Departament de Farmacologia i Toxicologia, Institut d'Investigacions Biomèdiques de Barcelona, Spain.
Neurotoxicol Teratol. 1997 Mar-Apr;19(2):117-27. doi: 10.1016/s0892-0362(96)00216-4.
The effects of subchronic 3,3'-iminodipropionitrile (IDPN) were characterized in the adult Long-Evans male rat. In a preparatory experiment, acute IDPN (890 mg/kg, IP) and intratympanic arsanilic acid caused similar alterations in locomotor activity, rearings, and scores for vestibular impairment. In a second preparatory experiment, IDPN in the drinking water (0%, 0.025%, 0.05%, 0.1%, 0.2%, or 0.4%) caused a concentration-dependent decrease in water intake, but a effective increase in IDPN intake. In the subchronic experiment, rats were exposed to the above concentrations of IDPN for 15 weeks, except the 0.4% group, exposed for only 7 weeks. Effects on body weight, motor activity, vestibular scores, vestibular morphology, and axonal diameter were observed after 0.2% and 0.4% IDPN. Proximal axonopathies but little or no clinical signs or vestibular toxicity followed 0.05% and 0.1% IDPN. We concluded that vestibular hair cell loss can be induced by subchronic IDPN at doses larger than the axonopathic doses, and that the vestibular toxicity, not the axonopathy, is responsible for the gross changes in behavior characterizing IDPN exposure.
研究了亚慢性3,3'-亚氨基二丙腈（IDPN）对成年雄性Long-Evans大鼠的影响。在一项预备实验中，急性IDPN（890 mg/kg，腹腔注射）和鼓膜内阿散酸对运动活动、竖毛行为和前庭损伤评分产生了相似的改变。在第二项预备实验中，饮用水中不同浓度的IDPN（0%、0.025%、0.05%、0.1%、0.2%或0.4%）导致饮水量呈浓度依赖性下降，但IDPN摄入量有效增加。在亚慢性实验中，大鼠暴露于上述浓度的IDPN中15周，但0.4%组仅暴露7周。观察了0.2%和0.4% IDPN对体重、运动活动、前庭评分、前庭形态和轴突直径的影响。0.05%和0.1% IDPN导致近端轴突病，但几乎没有临床症状或前庭毒性。我们得出结论，亚慢性IDPN在高于轴突病剂量时可诱导前庭毛细胞丢失，并且IDPN暴露所致行为的总体变化是由前庭毒性而非轴突病引起的。
