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

Abstract

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 ~ 80X faster in the nervous system (14 milliseconds 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 macaca fascicularis, plasma CDC changed proportionally to total proteins (r=0.43; p<0.001). The plasma CDC was ~ 2X 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.

Lower sulfurtransferase detoxification rates of cyanide in konzo—A tropical spastic paralysis linked to cassava cyanogenic poisoning

“…Children with konzo required up to 1670 ms to produce one μmol of SCN/mg protein in their plasma, which is about one-third the rate of that observed in non-human primates macaca fascicularis or two-thirds the rate of that observed in rodents. Detoxification rates in children without konzo were up to 1050 ms/μmolSCN/mg protein, which are equivalent to the rates reported for rodents (Kimani et al, 2014). Despite the lack of statistical significance, stunted children may detoxify cyanide faster than those who are not stunted.…”

“…In this respect, field-relevant (point-of-care) diagnostic tools to monitor risks in relation to cyanide exposure and metabolism are needed. Whether lower detoxification rates are mediated through genetics, deficiencies in select nutrients, or metabolic changes induced by cyanide or related metabolites such as the cyanide metabolite and carbamoylating agent cyanate has yet to be determined (Tshala-Katumbay et al, 2013; Makila-Mabe et al, 2014; Billaut-Laden et al, 2006a, b; Kimani et al, 2014; Banea-Mayambu et al, 2000; Kraus and Kraus, 2001). The potential for sustained and repeated neurotoxic injuries in subjects living in konzo areas warrants studies to assess the global burden of disease associated with chronic dietary reliance on cyanogenic cassava as the main source of food.…”

Subchronic cyanide toxicity on male reproductive system of albino rat

“…8,[11][12][13] Rao et al 14 reported that globally, 26 000 people are exposed to cyanogens every day; these compounds release toxic levels of cyanide ions in the body. [17][18][19][20] However, with the help of another mitochondrial enzyme rhodanase, lower doses of cyanide can get detoxified from the body without causing any harm. 1,15,16 In fact, only free cyanide (i.e., the sum of molecular hydrogen cyanide, HCN, and the cyanide anion, CN − ) is considered to be a biologically meaningful expression of cyanide toxicity, regardless of its origin.…”

“…Consequently, Bradbury et al 10 found higher level of thiocyanate (SCN − ) in school children consuming more cassava at the time of cassava harvest. 15,20,27,28 Therefore, based on the literature review, the present study was executed to examine the hypothesis; subchronic exposure of cyanide may affect the male reproductive system in Wister albino rats. 21,22 Studies demonstrated that cyanide affect spermatogenesis via the hypothalamic-pituitary-gonadal axis in male rainbow trout.…”

El Niño-southern oscillations and lathyrism epidemics

“…Linamarin (Sreeja et al, 2003), the cyanogenic glycoside in cassava, cyanohydrin (Soler-Martin et al, 2010), the breakdown product of linamarin, cyanide (Kimani et al, 2014), which is released from cyanohydrin, and several metabolites of cyanide, which include cyanate (Tor-Agbidye et al, 1999;Kimani et al, 2014), and iminothiazolidine-4-carboxylic acid (Bitner et al, 1995) have been investigated in experimental studies, but none have induced lesions consistent konzo. Thiocyanate (SCN − ), the major metabolite of cyanide, is considered the most likely neurotoxicant of konzo (Spencer, 1999; ( Figure 6C).…”