Broderick Kate E, Potluri Prasanth, Zhuang Shunhui, Scheffler Immo E, Sharma Vijay S, Pilz Renate B, Boss Gerry R
Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0652, USA.
Exp Biol Med (Maywood). 2006 May;231(5):641-9. doi: 10.1177/153537020623100519.
Cyanide is a highly toxic agent that inhibits mitochondrial cytochrome-c oxidase, thereby depleting cellular ATP. It contributes to smoke inhalation deaths in fires and could be used as a weapon of mass destruction. Cobalamin (vitamin B12) binds cyanide with a relatively high affinity and is used in Europe to treat smoke inhalation victims. Cobinamide, the penultimate compound in cobalamin biosynthesis, binds cyanide with about 10(10) greater affinity than cobalamin, and we found it was several-fold more effective than cobalamin in (i) reversing cyanide inhibition of oxidative phosphorylation in mammalian cells; (ii) rescuing mammalian cells and Drosophila melanogaster from cyanide toxicity; and (iii) reducing cyanide inhibition of Drosophila Malpighian tubule secretion. Cobinamide could be delivered by oral ingestion, inhalation, or injection to Drosophila, and it was as effective when administered up to 5 mins post-cyanide exposure as when given pre-exposure. We conclude that cobinamide is an effective cyanide detoxifying agent that has potential use as a cyanide antidote, both in smoke inhalation victims and in persons exposed to cyanide used as a weapon of mass destruction.
氰化物是一种剧毒物质，它会抑制线粒体细胞色素c氧化酶，从而耗尽细胞内的三磷酸腺苷（ATP）。它是火灾中导致吸入烟雾死亡的一个因素，并且可能被用作大规模杀伤性武器。钴胺素（维生素B12）以相对较高的亲和力与氰化物结合，在欧洲被用于治疗吸入烟雾的受害者。腺苷钴胺，钴胺素生物合成中的倒数第二个化合物，与氰化物的结合亲和力比钴胺素高约10的10次方，并且我们发现它在以下几个方面比钴胺素有效几倍：（i）逆转氰化物对哺乳动物细胞氧化磷酸化的抑制作用；（ii）使哺乳动物细胞和黑腹果蝇免受氰化物毒性的影响；（iii）减轻氰化物对果蝇马氏管分泌的抑制作用。腺苷钴胺可以通过口服、吸入或注射的方式给予果蝇，并且在氰化物暴露后5分钟内给药与暴露前给药的效果相同。我们得出结论，腺苷钴胺是一种有效的氰化物解毒剂，在吸入烟雾的受害者以及接触用作大规模杀伤性武器的氰化物的人员中都有作为氰化物解毒剂的潜在用途。
