Tanii H, Hashimoto K, Harada A
Department of Hygiene, School of Medicine, Kanazawa University, Japan.
Environ Res. 1993 Apr;61(1):140-9. doi: 10.1006/enrs.1993.1058.
Allylnitrile is known to induce head twitching in rats and mice. Carbon tetrachloride (CCl4) impairs the hepatic mixed function oxidase system and lowers acute toxicity of nitriles. In the present study we examined the effect of CCl4 on the allylnitrile-induced head twitching to elucidate the mechanism of the abnormal behavior. In rats, CCl4 pretreatment inhibited the head twitching induced by allylnitrile (1.49 mmole/kg, po), the maximal and dose-dependent inhibition occurring when CCl4 was given just prior to the nitrile administration, while CCl4 post-treatment had no effect on the head twitching. A dose-dependent inhibition of cyanide formation arising from allylnitrile in the liver and a dose-dependent attenuation of acute toxicity of allylnitrile were observed when CCl4 was given just prior to the nitrile administration in rats and mice. Intracerebroventricular injection of allylnitrile (2.0 to 18 mumole/brain) induced no head twitching in rats. The results suggest that active metabolites of allylnitrile are responsible for the head twitching, and that CCl4 prevents the metabolic process in the liver by forming conjugates with allylnitrile, resulting in the inhibition of the head twitching.
已知烯丙腈会诱发大鼠和小鼠头部抽搐。四氯化碳（CCl4）会损害肝脏混合功能氧化酶系统并降低腈类的急性毒性。在本研究中，我们检测了CCl4对烯丙腈诱发的头部抽搐的影响，以阐明异常行为的机制。在大鼠中，CCl4预处理可抑制烯丙腈（1.49毫摩尔/千克，口服）诱发的头部抽搐，当在给予腈类药物之前立即给予CCl4时，会出现最大且呈剂量依赖性的抑制作用，而CCl4后处理对头部抽搐没有影响。当在大鼠和小鼠中在给予腈类药物之前立即给予CCl4时，观察到肝脏中烯丙腈产生的氰化物形成呈剂量依赖性抑制，且烯丙腈的急性毒性呈剂量依赖性减弱。脑室内注射烯丙腈（2.0至18微摩尔/脑）未在大鼠中诱发头部抽搐。结果表明，烯丙腈的活性代谢产物是导致头部抽搐的原因，并且CCl4通过与烯丙腈形成结合物来阻止肝脏中的代谢过程，从而导致头部抽搐受到抑制。
