Cyanide and the human brain: perspectives from a model of food (cassava) poisoning

Abstract

Threats by fundamentalist leaders to use chemical weapons have resulted in renewed interest in cyanide toxicity. Relevant insights may be gained from studies on cyanide mass intoxication in populations relying on cyanogenic cassava as the main source of food. In these populations, sublethal concentrations (up to 80 µmol/L) of cyanide in the blood are commonplace and lead to signs of acute toxicity. Long-term toxicity signs include a distinct and irreversible spastic paralysis, known as konzo, and cognition deficits, mainly in sequential processing (visual–spatial analysis) domains. Toxic culprits include cyanide (mitochondrial toxicant), thiocyanate (AMPA-receptor chaotropic cyanide metabolite), cyanate (protein-carbamoylating cyanide metabolite), and 2-iminothiazolidine-4-carboxylic acid (seizure inducer). Factors of susceptibility include younger age, female gender, protein-deficient diet, and, possibly, the gut functional metagenome. The existence of uniquely exposed and neurologically affected populations offers invaluable research opportunities to develop a comprehensive understanding of cyanide toxicity and test or validate point-of-care diagnostic tools and treatment options to be included in preparedness kits in response to cyanide-related threats.

Cognitive and motor performance in Congolese children with konzo during 4 years of follow-up: a longitudinal analysis

“…However, in view of what is known from the evidence about the probable neuropathogenic mechanisms of brain toxicity from cyanogenic toxins in poorly processed cassava, the neurocognitive effects of thiamine and other vitamin deficiencies in konzo are likely to be secondary to these. 2 , 13 Regardless, the role of such micronutrient deficiencies as they relate to the direct neuropathogenic processes from cassava cyanogen exposure in nutritionally at-risk children with konzo is a key priority for future research, particularly because these factors relate to gender differences for konzo risk and progression.…”

“…Both the KABC-II and BOT-2 were used in this follow-up assessment because they also proved sensitive to metabolic biomarkers of cyanide exposure from poorly processed cassava in the baseline assessment. 11 – 13 …”

“…As such, this measure is only a general indication of cassava processing practices in the household at that time, and cannot be considered a sensitive biomarker to past exposure or cumulative exposure to poorly processed cassava. 13 , 14 Baseline urinary thiocyanate was assessed for the groups with konzo (mean 519 µmol/L, SD 354) and without konzo (mean 389 µmol/L, SD 224). These concentrations represent high cyanogenic exposure in both groups for this time of year, based on earlier studies by Banea and colleagues 15 , 16 of thiocyanate levels among konzo-affected populations in this region.…”

Basic Biology of Hypoxic Responses Mediated by the Transcription Factor HIFs and Its Implication for Medicine

“…Such a disease state may be caused by tissue O 2 metabolism disorder. Conditions that suppress O 2 metabolism in cells, such as cytotoxicity, mitochondrial suppression via therapeutic drugs or cyanide poisoning [22,23], biguanide-induced lactate acidosis [24,25] and propofol infusion syndrome [26,27], are classified in this category. However, oxygen metabolism disorder cannot be accurately diagnosed in real-time prior to organ dysfunction or some such effect becoming apparent.…”

Cassava Cultivars Response to Different Levels of Potassium Fertilization under Drip Irrigation and Sandy Soil Conditions

“…The wastes derived-cassava could be used also in the biorefinery and industrial applications (Zhang et al 2016 andde Carvalho et al 2018), which could mitigate the carbon emission and save the energy (Jiang et al 2019). Cassava crop has some problems including the short postharvest shelf-life about 1-3 days (Uchechukwu-Agua et al 2015;Djabou et al 2017), the low protein content and the high content of cyanogenic compounds (Tshala-Katumbay et al 2016), and existence of anti-nutrients in its tissues like tannins, polyphenols andphytic acid (Hawashi et al 2019). Otherwise, this crop may be favor under small-and large-scale cultivation (Li et al 2017).…”