Abstract
We sought to determine whether motor and cognitive deficits associated with cassava (food) cyanogenic poisoning were associated with high concentrations of F2-isoprostanes, well-established indicators of oxidative damage. Concentrations of serum F2-isoprostanes were quantified by LC-MS/MS and anchored to measures of motor proficiency and cognitive performance, which were respectively assessed through BOT-2 (Bruininks/Oseretsky Test, 2nd Edition) and KABC-II (Kaufman Assessment Battery for Children, 2nd edition) testing of 40 Congolese children (21 with konzo and 19 presumably healthy controls, overall mean age (SD): 9.3 (3.2) years). Exposure to cyanide was ascertained by concentrations of its main metabolite thiocyanate (SCN) in plasma and urine. Overall, SCN concentrations ranged from 91 to 325 and 172 to 1032 µmol/l in plasma and urine, respectively. Serum isoprostanes ranged from 0.1 to 0.8 (Isoprostane-III), 0.8 to 8.3 (total Isoprostane-III), 0.1 to 1.5 (Isoprostane-VI), 2.0 to 9.0 (total Isoprostane-VI), or 0.2 to 1.3 ng/ml (8,12-iso-iPF2α-VI isoprostane). Children with konzo poorly performed at the BOT-2 and KABC-II testing relative to presumably healthy children (p<0.01). Within regression models adjusting for age, gender, motor proficiency, and other biochemical variables, 8,12-iso-iPF2α-VI isoprostane was significantly associated with the overall cognitive performance (β = −32.36 (95% CI: −51.59 to −13.03; P<0.001). This model explained over 85% of variation of the KABC-II score in children with konzo, but was not significant in explaining the motor proficiency impairment. These findings suggest that cognitive deficits and, possibly, brain injury associated with cassava poisoning is mediated in part by oxidative damage in children with konzo. 8,12-iso-iPF2α-VI isoprostane appears to be a good marker of the neuropathogenic mechanisms of konzo and may be used to monitor the impact of interventional trials to prevent the neurotoxic effects of cassava cyanogenic poisoning.
Highlights
Chronic reliance on cyanogenic cassava (a.k.a manioc or tapioca) as staple food and poor nutrition have been incriminated in the etiology of konzo, tropical ataxic neuropathy (TAN), and, reportedly, a motor neuron-cerebellar-parkinson-dementia syndrome (MNCPD) among rural populations of sub-Saharan Africa [1,2,3,4,5,6,7]
While there is a substantial body of knowledge on the markers of susceptibility to cassava cyanogenic poisoning and related neurological deficits, little is known on the biomarkers of the neuropathological processes, potential targets of efforts to prevent the development of the aforementioned deficits once the children have been exposed to cyanogenic compounds arising from consumption of poorly processed cyanogenic cassava [5]
The Biomarkers of Oxidative Stress (BOSS) Study, an independent and multi-investigator study sponsored by the National Institute of Environmental Health Sciences has determined that the most accurate method to assess in vivo oxidative stress status is to quantify plasma or urinary free isoprostanes (F2-IsoPs), which are by-products of non-enzymatic oxidative damage of lipids [18,19,20]
Summary
Chronic reliance on cyanogenic cassava (a.k.a manioc or tapioca) as staple food and poor nutrition have been incriminated in the etiology of konzo, tropical ataxic neuropathy (TAN), and, reportedly, a motor neuron-cerebellar-parkinson-dementia syndrome (MNCPD) among rural populations of sub-Saharan Africa [1,2,3,4,5,6,7]. Previous studies including experimental modeling of cyanide poisoning have suggested that oxidative damage may play a central role in the pathogenesis of cassava-associated neurological deficits [14,15,16]. Such indication has been lacking for in-vivo human studies on konzo, a condition with a myriad of etiological factors with a potential to trigger a massive oxidative response. These include but not limited to the direct toxicity of cyanide on mitochondria, a major source of reactive oxygen species (ROS), which can cause oxidative damage and cell death [5]. We sought to determine whether the motor and cognitive deficits associated with cassava (food) cyanogenic poisoning were associated with high concentrations of F2-IsoPs
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
