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Cyanide detoxification by the cobalamin precursor cobinamide.

Kate E Broderick1, Prasanth Potluri, Shunhui Zhuang

  • 1Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0652, USA.

Experimental Biology and Medicine (Maywood, N.J.)
|April 26, 2006
PubMed
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Cobinamide, a vitamin B12 precursor, is a potent cyanide detoxifier. It effectively reverses cyanide toxicity in cells and organisms, showing promise as a cyanide antidote for various exposures.

Area of Science:

  • Biochemistry
  • Toxicology
  • Pharmacology

Background:

  • Cyanide is a potent toxin inhibiting cellular respiration.
  • Cyanide poisoning is a significant cause of fire-related deaths and a potential bioterrorism threat.
  • Cobalamin (vitamin B12) is used clinically to treat cyanide exposure.

Purpose of the Study:

  • To evaluate cobinamide as a cyanide antidote.
  • To compare the efficacy of cobinamide and cobalamin in cyanide detoxification.
  • To assess cobinamide's effectiveness in various exposure scenarios and administration routes.

Main Methods:

  • Assessing cobinamide's reversal of cyanide-induced inhibition of oxidative phosphorylation in mammalian cells.
  • Testing cobinamide's efficacy in rescuing mammalian cells and Drosophila melanogaster from cyanide toxicity.

Related Experiment Videos

  • Investigating cobinamide's effect on cyanide-inhibited Drosophila Malpighian tubule secretion.
  • Evaluating cobinamide administration via oral, inhalation, and injection routes in Drosophila.

    • Main Results:

    • Cobinamide binds cyanide with significantly higher affinity than cobalamin.
    • Cobinamide was several-fold more effective than cobalamin in reversing cyanide toxicity in cellular and organismal models.
    • Cobinamide demonstrated efficacy when administered up to 5 minutes post-cyanide exposure.
    • Effective delivery of cobinamide was achieved through oral, inhalation, and injection routes in Drosophila.

    Conclusions:

    • Cobinamide is a highly effective agent for cyanide detoxification.
    • Cobinamide shows significant potential as a cyanide antidote for smoke inhalation and weaponized cyanide exposure.
    • Cobinamide's efficacy and versatile administration routes support its development as a clinical countermeasure.