Broderick Kate E, Balasubramanian Maheswari, Chan Adriano, Potluri Prasanth, Feala Jake, Belke Darrell D, McCulloch Andrew, Sharma Vijay S, Pilz Renate B, Bigby Timothy D, Boss Gerry R
Department of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0652, USA.
Exp Biol Med (Maywood). 2007 Jun;232(6):789-98.
Sodium nitroprusside is used to treat hypertensive emergencies and acute heart failure. It acts by releasing nitric oxide (NO), a highly potent vasodilator, but unfortunately, for each NO molecule released, five cyanide ions are released. Thus, nitroprusside therapy is limited by cyanide toxicity. Therefore, a cyanide scavenger could be beneficial when administering nitroprusside. Hydroxocobalamin, which has a relatively high binding affinity for cyanide, has been shown to reduce cyanide levels in nitroprusside-treated patients. Cobinamide, the penultimate precursor in hydroxocobalamin biosynthesis, has a much greater affinity for cyanide than cobalamin, and binds two cyanide ions. We now show that cobinamide is highly effective in neutralizing cyanide ions released by nitroprusside in cultured mammalian cells, Drosophila melanogaster, and mice. Cobinamide also binds NO, but at molar concentrations 2.5-5 times that of nitroprusside, it did not decrease NO concentrations or the physiological effectiveness of nitroprusside. We conclude that cobinamide could be a valuable adjunct to nitroprusside therapy.
硝普钠用于治疗高血压急症和急性心力衰竭。它通过释放一氧化氮（NO）起作用，一氧化氮是一种强效血管扩张剂，但不幸的是，每释放一个NO分子，就会释放出五个氰离子。因此，硝普钠治疗受到氰化物毒性的限制。所以，在使用硝普钠时，氰化物清除剂可能会有帮助。羟钴胺对氰化物具有相对较高的结合亲和力，已被证明可降低接受硝普钠治疗患者的氰化物水平。钴胺酰胺是羟钴胺生物合成的倒数第二个前体，对氰化物的亲和力比钴胺素大得多，并且能结合两个氰离子。我们现在表明，钴胺酰胺在培养的哺乳动物细胞、黑腹果蝇和小鼠中能高效中和硝普钠释放的氰离子。钴胺酰胺也能结合NO，但在摩尔浓度为硝普钠的2.5至5倍时，它不会降低NO浓度或硝普钠的生理效力。我们得出结论，钴胺酰胺可能是硝普钠治疗的一种有价值的辅助药物。
