The cobalamin precursor cobinamide detoxifies nitroprusside-generated cyanide.
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.
Broderick
Kate E
KE
Department of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0652, USA.
Balasubramanian
Maheswari
M
Chan
Adriano
A
Potluri
Prasanth
P
Feala
Jake
J
Belke
Darrell D
DD
McCulloch
Andrew
A
Sharma
Vijay S
VS
Pilz
Renate B
RB
Bigby
Timothy D
TD
Boss
Gerry R
GR
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D002478:Cells, Cultured; D003038:Cobamides / Q000494:pharmacology*; D003486:Cyanides / Q000378:metabolism*; D004331:Drosophila melanogaster; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008317:Malpighian Tubules / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D009599:Nitroprusside / Q000493:pharmacokinetics* / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D011651:Pulmonary Artery / Q000166:cytology; D051381:Rats; D013861:Thiocyanates / Q000097:blood / Q000652:urine; D014805:Vitamin B 12
D000959:Antihypertensive Agents; D003038:Cobamides; D003486:Cyanides; D009566:Nitrates; D009573:Nitrites; D013861:Thiocyanates; C017142:cobinamide; D009599:Nitroprusside; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; C031760:thiocyanate; D014805:Vitamin B 12