title: Serum 8,12-iso-iPF2α-VI isoprostane marker of oxidative damage and cognition deficits in children with konzo.
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.
authors.affiliation: Department of Neurology, University of Kinshasa, Kinshasa, Congo-Kinshasa.
authors.forename: Bumoko G
authors.initials: BG
authors.lastname: Makila-Mabe
authors.affiliation: Department of Biomedical Sciences, University of Kinshasa, Kinshasa, Congo-Kinshasa.
authors.forename: Kambale J
authors.initials: KJ
authors.lastname: Kikandau
authors.affiliation: Department of Neurology, University of Kinshasa, Kinshasa, Congo-Kinshasa.
authors.forename: Thérèse M
authors.initials: TM
authors.lastname: Sombo
authors.affiliation: Department of Neurology, University of Kinshasa, Kinshasa, Congo-Kinshasa.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Okitundu
authors.affiliation: Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Mwanza
authors.affiliation: Department of Psychiatry and Neurology/Ophthalmology, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Boivin
authors.affiliation: Department of Tropical Medicine, University of Kinshasa, Kinshasa, Congo-Kinshasa; Department of Parasitology, Institut National de Recherches Biomédicales, Kinshasa, Congo-Kinshasa.
authors.forename: Mumba D
authors.initials: MD
authors.lastname: Ngoyi
authors.affiliation: Department of Tropical Medicine, University of Kinshasa, Kinshasa, Congo-Kinshasa; Department of Parasitology, Institut National de Recherches Biomédicales, Kinshasa, Congo-Kinshasa.
authors.forename: Jean-Jacques T
authors.initials: JJ
authors.lastname: Muyembe
authors.affiliation: Department of Nutrition, School of Public Health & National Nutrition Program, Ministry of Health, Kinshasa, Congo-Kinshasa.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Banea
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Gerard R
authors.initials: GR
authors.lastname: Boss
authors.affiliation: Department of Neurology, University of Kinshasa, Kinshasa, Congo-Kinshasa; Department of Neurology, Oregon Health & Science University, Portland, Oregon, United States of America; Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Desiré
authors.initials: D
authors.lastname: Tshala-Katumbay
mesh_terms: D015415:Biomarkers / Q000097:blood; D002648:Child; D002853:Chromatography, Liquid; D003071:Cognition; D028441:F2-Isoprostanes / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D002365:Manihot / Q000378:metabolism / Q000506:poisoning*; D018384:Oxidative Stress; D053719:Tandem Mass Spectrometry; D013861:Thiocyanates / Q000097:blood
chemical_list: D015415:Biomarkers; D028441:F2-Isoprostanes; D013861:Thiocyanates; C031760:thiocyanate