Accession Number : ADA256062


Title :   Development of Biochemical Cyanide Antidotes.


Descriptive Note : Final rept. Feb 1989-Jan 1992,


Corporate Author : PURDUE UNIV RESEARCH FOUNDATION LAFAYETTE IN DIV OF SPONSORED PROGRAMS


Personal Author(s) : Isom, Gary E ; Borowitz, Joseph L


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a256062.pdf


Report Date : 01 Mar 1992


Pagination or Media Count : 42


Abstract : A series of six biochemical markers of cyanide toxicity (dopamine release, peroxide generation, cytosolic-free calcium, catalase activity, cytochrome oxidase activity and superoxide dismutase activity) in cultured rat pheochromocytoma (PC12) cells were used to establish a screen for evaluation of potential anticyanide compounds. Thirty-nine substances, including anticonvulsants, adrenergic blockers, antioxidants, antipsychotics, etc., were tested and ranked according to the results. Based on the composite scoring in all six assays, carbamazepine, mannitol, allopurinol and phenytoin were ranked as the most effective anticyanide compounds. Additionally, known cyanide antidotes (e.g., pyruvate, mercaptopyruvate, alpha ketoglutarate, naloxone and flunarizine) obtained relatively high ranking in the PC12 cell screen. Furthermore, a significant correlation was found between protective effects (based on LD50s) of cyanide antidotes in mice and ranking in the in vitro screen. This study illustrates that by assaying a series of biochemical markers in a neuron-cell line, a rapid, cost-effective in vitro toxicological screen for cyanide antidotes is possible. Several compounds have been identified which inhibit the biochemical effects of cyanide and may be used to enhance effectiveness of the standard cyanide antidotes. Cyanide antidotes, PC12 cells, carbamazepine mannitol, allopurinol, in vitro screen, RA V, Cell culture.


Descriptors :   *BIOCHEMISTRY , *ANTIDOTES , *CYANIDES , CALCIUM , RATS , ENZYMES , COSTS , RELEASE , MICE , PEROXIDES , SUPEROXIDE DISMUTASE , ANTICONVULSANTS , ANTIOXIDANTS , SCORING , DOPAMINE , ASSAYING , CULTURE , RANKING , SUPEROXIDES , PYRUVATES , MANNITOL , CYTOCHROME OXIDASE , CATALASE , OXIDOREDUCTASES , MARKERS , NERVE CELLS , STANDARDS , CORRELATION , IN VITRO ANALYSIS , CELLS , TOXICITY


Subject Categories : Biochemistry
      Toxicology
      Pharmacology
      Inorganic Chemistry


Distribution Statement : APPROVED FOR PUBLIC RELEASE