神经毒性氨基腈在体内和体外的氰化物释放

In vivo and in vitro release of cyanide from neurotoxic aminonitriles.

作者信息

Froines J R, Postlethwait E M, LaFuente E J, Liu W C

出版信息

J Toxicol Environ Health. 1985;16(3-4):449-60. doi: 10.1080/15287398509530754.

Abstract

Cyanide release from neurotoxic aminonitriles was measured following in vitro incubation with both microsomes and liver slices. Investigation of cyanide released as urinary thiocyanate following ip aminonitrile administration to rats was also measured. The yield of cyanide in the in vivo study, as measured by the mole percent of administered dose, was greatest from dimethylaminonitrile (DMAA), followed by trimethylaminopropionitrile (TMAPN), dimethylaminopropionitrile (DMAPN), 3,3'-iminodipropionitrile (IDPN), dimethylaminobutyronitrile (DMABN), and monomethylaminopropionitrile (MMAPN). Urinary excretion of thiocyanate accounted for 48.9% of the administered DMAA, 11.6% of TMAPN, 8.0% of DMAPN, 6.8% of IDPN, 3.1% of DMABN, and 1.8% of MMAPN. Incubation of aminonitriles and related compounds with microsomes or liver slices from rats yielded measurable quantities of cyanide from all the compounds tested except for DMABN, TMABN, and succiononitrile. Quantitative evaluation of the yield of formaldehyde by demethylation following microsomal incubation was also determined. The signs of acute toxicity in rats after ip administration of KCN were similar only to those in rats administered DMAA.

摘要

在与微粒体和肝切片进行体外孵育后，测定了神经毒性氨基腈中氰化物的释放量。还测定了对大鼠腹腔注射氨基腈后，作为尿硫氰酸盐释放的氰化物。在体内研究中，以给药剂量的摩尔百分比衡量，氰化物产量最高的是二甲基氨基腈（DMAA），其次是三甲基氨基丙腈（TMAPN）、二甲基氨基丙腈（DMAPN）、3,3'-亚氨基二丙腈（IDPN）、二甲基氨基丁腈（DMABN）和单甲基氨基丙腈（MMAPN）。硫氰酸盐的尿排泄量分别占给药DMAA的48.9%、TMAPN的11.6%、DMAPN的8.0%、IDPN的6.8%、DMABN的3.1%和MMAPN的1.8%。氨基腈及相关化合物与大鼠微粒体或肝切片孵育后，除DMABN、TMABN和琥珀腈外，所有测试化合物均产生了可测量的氰化物量。还测定了微粒体孵育后通过去甲基化产生甲醛的产量的定量评估。腹腔注射KCN后大鼠的急性毒性体征仅与注射DMAA的大鼠相似。