Cross-species and tissue variations in cyanide detoxification rates in rodents and non-human primates on protein-restricted diet

•Mammals display a differential pattern of cyanide detoxification capabilities (CDC) across species and tissues.•Plasma CDC decreases in proportion to total plasma proteins in non-human primates.•Nervous system CDC may be impaired by dietary deficiency in sulfur amino acids and/or exposure to cyanide or cyanate.•Susceptibility to cyanide poisoning may be modified by diet and endogenous tissue variations in CDC.

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 (2.5 mg/kg bw) or NaOCN (50 mg/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.