Sulfanegen sodium treatment in a rabbit model of sub-lethal cyanide toxicity

Matthew Brenner, Jae G. Kim, Jangwoen Lee, Sari B. Mahon, Daniel Lemor, Rebecca Ahdout, Gerry R. Boss, William Blackledge, Lauren Jann, Herbert T. Nagasawa, Steven Patterson

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

The aim of this study is to investigate the ability of intramuscular and intravenous sulfanegen sodium treatment to reverse cyanide effects in a rabbit model as a potential treatment for mass casualty resulting from cyanide exposure. Cyanide poisoning is a serious chemical threat from accidental or intentional exposures. Current cyanide exposure treatments, including direct binding agents, methemoglobin donors, and sulfur donors, have several limitations. Non-rhodanese mediated sulfur transferase pathways, including 3-mercaptopyruvate sulfurtransferase (3-MPST) catalyze the transfer of sulfur from 3-MP to cyanide, forming pyruvate and less toxic thiocyanate. We developed a water-soluble 3-MP prodrug, 3-mercaptopyruvatedithiane (sulfanegen sodium), with the potential to provide a continuous supply of substrate for CN detoxification. In addition to developing a mass casualty cyanide reversal agent, methods are needed to rapidly and reliably diagnose and monitor cyanide poisoning and reversal. We use non-invasive technology, diffuse optical spectroscopy (DOS) and continuous wave near infrared spectroscopy (CWNIRS) to monitor physiologic changes associated with cyanide exposure and reversal. A total of 35 animals were studied. Sulfanegen sodium was shown to reverse the effects of cyanide exposure on oxyhemoglobin and deoxyhemoglobin rapidly, significantly faster than control animals when administered by intravenous or intramuscular routes. RBC cyanide levels also returned to normal faster following both intramuscular and intravenous sulfanegen sodium treatment than controls. These studies demonstrate the clinical potential for the novel approach of supplying substrate for non-rhodanese mediated sulfur transferase pathways for cyanide detoxification. DOS and CWNIRS demonstrated their usefulness in optimizing the dose of sulfanegen sodium treatment.

Original languageEnglish (US)
Pages (from-to)269-276
Number of pages8
JournalToxicology and Applied Pharmacology
Volume248
Issue number3
DOIs
StatePublished - Nov 1 2010

Bibliographical note

Funding Information:
This Research Project was partially sponsored by the NIH , with grant numbers 1U54NS063718-01 and U01-NS058030 , AF [ 9550-01-1-0101 , 9550-08-1-0384 ] and the Laser Microbeam and Medical Program from the National Center for Research Resources [ P41RR001192 ].

Keywords

  • Chemical and biological weapons
  • Cyanide toxicity reversal
  • Optical hemodynamic monitoring

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