Cross-species and tissue variations in cyanide detoxification rates in rodents and non-human primates on protein-restricted diet.
We sought to elucidate the impact of diet, cyanide or cyanate exposure on mammalian cyanide detoxification capabilities (CDC). Male rats (~8 weeks old) (N=52) on 75% sulfur amino acid (SAA)-deficient diet were treated with NaCN (2.5mg/kg bw) or NaOCN (50mg/kg bw) for 6 weeks. Macaca fascicularis monkeys (~12 years old) (N=12) were exclusively fed cassava for 5 weeks. CDC was assessed in plasma, or spinal cord, or brain. In rats, NaCN induced seizures under SAA-restricted diet whereas NaOCN induced motor deficits. No deficits were observed in non-human primates. Under normal diet, the CDC were up to ~80× faster in the nervous system (14 ms to produce one μmol of thiocyanate from the detoxification of cyanide) relative to plasma. Spinal cord CDC was impaired by NaCN, NaOCN, or SAA deficiency. In M. fascicularis, plasma CDC changed proportionally to total proteins (r=0.43; p<0.001). The plasma CDC was ~2× relative to that of rodents. The nervous system susceptibility to cyanide may result from a "multiple hit" by the toxicity of cyanide or its cyanate metabolite, the influences of dietary deficiencies, and the tissue variations in CDC. Chronic dietary reliance on cassava may cause metabolic derangement including poor CDC.
School of Nursing Sciences, University of Nairobi, Kenya; Department of Pharmacology and Pharmacognosy, University of Nairobi, Kenya.
S
S
Kimani
Department of Comparative Medicine, Oregon Health & Science University (OHSU), USA.
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V
Moterroso
Mannheimer Foundation, Inc., Homestead, FL, USA.
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P
Morales
Mannheimer Foundation, Inc., Homestead, FL, USA.
J
J
Wagner
Department of Pharmacology and Pharmacognosy, University of Nairobi, Kenya.
S
S
Kipruto
Department of Medical Physiology, University of Nairobi, Kenya.
F
F
Bukachi
Department of Pharmacology and Pharmacognosy, University of Nairobi, Kenya.
C
C
Maitai
Oregon Institute of Occupational Health Sciences, OHSU, USA; Department of Neurology, OHSU, USA. Electronic address: tshalad@ohsu.edu.
D
D
Tshala-Katumbay
D000818:Animals; D003486:Cyanides / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D004044:Dietary Proteins / Q000008:administration & dosage*; D008252:Macaca fascicularis; D008297:Male; D051381:Rats; D013045:Species Specificity
D003486:Cyanides; D004044:Dietary Proteins
Cassava; Cyanate; Cyanide; Konzo; Neurotoxicity; Rhodanese