Bioactivation of cyanide to cyanate in sulfur amino acid deficiency: relevance to neurological disease in humans subsisting on cassava.
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.
Tor-Agbidye
J
J
Center for Research on Occupational and Environmental Toxicology, Oregon Health Sciences University, Portland 97201, USA.
Palmer
V S
VS
Lasarev
M R
MR
Craig
A M
AM
Blythe
L L
LL
Sabri
M I
MI
Spencer
P S
PS
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003485:Cyanates / Q000097:blood*; D003486:Cyanides / Q000097:blood*; D003553:Cystine / Q000172:deficiency*; D004231:Diuresis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D002365:Manihot / Q000633:toxicity; D008715:Methionine / Q000172:deficiency*; D011190:Potassium Cyanide / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013431:Sulfates / Q000652:urine; D013861:Thiocyanates / Q000652:urine; D013997:Time Factors
D003485:Cyanates; D003486:Cyanides; D013431:Sulfates; D013861:Thiocyanates; D003553:Cystine; D008715:Methionine; D011190:Potassium Cyanide