Bioactivation of cyanide to cyanate in sulfur amino acid deficiency: relevance to neurological disease in humans subsisting on cassava.

TitleBioactivation of cyanide to cyanate in sulfur amino acid deficiency: relevance to neurological disease in humans subsisting on cassava.
Publication TypeJournal Article
Year of Publication1999
AuthorsTor-Agbidye J, Palmer VS, Lasarev MR, Craig AM, Blythe LL, Sabri MI, Spencer PS
JournalToxicological sciences : an official journal of the Society of Toxicology
Volume50
Issue2
Pagination228-35
Date Published1999 Aug
ISSN1096-6080
KeywordsAnimals, Body Weight, Cyanates, Cyanides, Cystine, Diuresis, Dose-Response Relationship, Drug, Female, Humans, Manihot, Methionine, Potassium Cyanide, Random Allocation, Rats, Rats, Sprague-Dawley, Sulfates, Thiocyanates, Time Factors
Abstract

Neurological disorders have been reported from parts of Africa with protein-deficient populations and attributed to cyanide (CN-) exposure from prolonged dietary use of cassava, a cyanophoric plant. Cyanide is normally metabolized to thiocyanate (SCN-) by the sulfur-dependent enzyme rhodanese. However, in protein-deficient subjects where sulfur amino acids (SAA) are low, CN may conceivably be converted to cyanate (OCN-), which is known to cause neurodegenerative disease in humans and animals. This study investigates the fate of potassium cyanide administered orally to rats maintained for up to 4 weeks on either a balanced diet (BD) or a diet lacking the SAAs, L-cystine and L-methionine. In both groups, there was a time-dependent increase in plasma cyanate, with exponential OCN- increases in SAA-deficient rats. A strongly positive linear relationship between blood CN- and plasma OCN- concentrations was observed in these animals. These data are consistent with the hypothesis that cyanate is an important mediator of chronic cyanide neurotoxicity during protein-calorie deficiency. The potential role of thiocyanate in cassava-associated konzo is discussed in relationship to the etiology of the comparable pattern of motor-system disease (spastic paraparesis) seen in lathyrism.

Alternate JournalToxicol. Sci.