Zinc, a Neurotoxin to Cultured Neurons, Contaminates Cycad Flour Prepared by Traditional Guamanian Methods (original) (raw)
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Journal of analytical toxicology
Over the past 30 years there have been attempts to link the unusually high incidence of amyotrophic lateral sclerosis (ALS) among the Chamorros native to the island of Guam to the consumption of the seeds of Cycas circinafis L., the false sago palm. In support of this relationship it was recently shown that, when given to primates, 2-amino-3-(methylamino)-propanoic acid (BMAA), a minor cycad component, can cause selective degeneration of upper and lower motor neurons in the spinal cord and clinical features similar to those of ALS. In order to test the relationship between ALS and cycads, we have developed a sensitive and precise gas chromatographic/mass spectrometric (GC/MS) assay for BMAA which allows direct assessment of the BMAA content in foods and is directly applicable to the assay of BMAA in biologic tissues and fluids. After the addition of a deuterated isotopomer as an internal standard and transesterication with 2-methyl-l-propanol, BMAA was extracted into dichloromethane and then acylated with pentafluoropropionic anhydride before GC/MS. This method permits precise quantlfcation of BMAA in the low picogram/sample range. Direct quantification of the BMAA content in the female gametophyte tissue (endosperm) of a range of cycad seeds collected from Guam confirmed the presence of BMAA at levels of approximately 1 mg/g (dry weight). The presence of BMAA in the seed extract was confirmed after derivatization of an aliquot of the extract and GC/MS analysis in the scanning mode. BMAA was found to be present, albeit at lower levels, in the endosperm of the seeds of C. revolufa (0.32 mg/g) and C. media (0.29 rag/g). Reproduction (photocopying) of editorial content of this journal is prohibited without publisher's permission,
Neurotoxicity of cassava cyanogens in rodents and non-human primates
2014
A thesis submitted in fulfillment of the requirements for the award of the degree of Doctor of Philosophy of the University of Nairobi. LIST OF ABBREVIATIONS AAA All amino acid AMPA α-amino-3-hydroxyl-5-methyl-4-Isoxazolepropionic acid; Class of glutamate receptor mediating fast excitatory CNS transmission CAA Carbamoyl-amino acids CAE Correct arm entries CDC Cyanide detoxification capabilities CN Cyanide CNS Central nervous system CROET DEFINITION OF TERMS Biomarkers: a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes (disease, infection, environmental exposure) , or pharmacologic responses to a therapeutic intervention Carbamoylation: a nonenzymatic posttranslational protein modification mediated by cyanate a cyanogenic analog. Carbamoylation reactions alters the structure, charge and functional properties of certain proteins and have been implicated directly in the underlying mechanisms of various diseases namely neurodegenerative conditions, atherosclerosis and inflammation. Cognition: a Set of all mental abilities and processes related to learning, memory, attention, judgment, evaluation, reasoning, problem solving, decision making and comprehension. In this study, working, long-term and reference memory were evaluated as evidence for cognition Cyanide detoxification capability (rate): the number of milliseconds required to produce one µmol of thiocyanate per mg of protein (ms/(µmol/mg) in the tested sample. Cyanogenesis: the ability of a plant to synthesize cyanogenic glycosides which liberate hydrogen cyanide upon hydrolysis. Konzo: is a non progressive, permanent upper motor neuron disease which occurs in an epidemic pattern among population that staple on cassava in Sub-Saharan Africa (WHO, 1996). Long term Memory: information that is useful in all exposures to the radial arm navigation task across all the days of testing
Animal Models of Brain Maldevelopment Induced by Cycad Plant Genotoxins
Cycads are long-lived tropical and subtropical plants that contain azoxyglycosides (e.g., cycasin, macrozamin) and neurotoxic amino acids (notably β-N-methylamino-l-alanine l-BMAA), toxins that have been implicated in the etiology of a disappearing neurodegenerative disease, amyotrophic lateral sclerosis and parkinsonism-dementia complex that has been present in high incidence among three genetically distinct populations in the western Pacific. The neuropathology of amyotrophic lateral sclerosis/parkinsonism-dementia complex includes features suggestive of brain maldevelopment, an experimentally proven property of cycasin attributable to the genotoxic action of its aglycone methylazoxymethanol (MAM). This property of MAM has been exploited by neurobiologists as a tool to study perturbations of brain development. Depending on the neurodevelopmental stage, MAM can induce features in laboratory animals that model certain characteristics of epilepsy, schizophrenia, or ataxia. Studies in DNA repair-deficient mice show that MAM perturbs brain development through a DNA damage-mediated mechanism. The brain DNA lesions produced by systemic MAM appear to modulate the expression of genes that regulate neurodevelopment and contribute to neurodegeneration. Epigenetic changes (histone lysine methylation) have also been detected in the underdeveloped brain after MAM administration. The DNA damage and epigenetic changes produced by MAM and, perhaps by chemically related substances (e.g., nitrosamines, nitrosoureas, hydrazines), might be an important mechanism by which early-life exposure to genotoxicants can induce long-term brain dysfunction.
HortScience
Consumption of Cycas micronesica seed tissue has been associated with the amyotrophic lateral sclerosis–parkinsonism dementia complex (ALS–PDC) of the Western Pacific. However, failures to document vital plant and neighborhood descriptors and pronounced variability in toxin concentrations noted within and among studies obfuscate decades of research on this subject. We discuss the theoretical and experimental constraints of plant tissue sampling in relation to human disease research. Comparisons are made between this approach and methods used throughout the history of ALS–PDC research, most notably very recent reports concerning β-methyl-amino-alanine. Methods for studying possible plant neurotoxins need to be standardized and must follow rigorous criteria to be valid in principle. Our discussions reveal why these criteria are essential and highlight the impact that natural variations have on environmental toxin quantification and interpretation. Past research on cycad toxins is defi...
Some Factors Affecting the Neurotoxic Effect of Palmyrah Flour
INTRODUCTION 1.1 General introduction 1.2 Justification and scope of study 5 2. LITERATURE REVIEW 2.1 General description of the palmyrah palm 6 2.2 Distribution of palmyrah palm 6 2.3 Production of palmyrah palm 9 2.4 Source of palmyrah flour 9 2.5 Odiyal flour 10 2.5.1 Composition 10 2.5.2 The microelement composition of odiyal flour 10 2.5.3 The amino acid composition of odiyal flour 10 2.5.4 The metal ion content 2.6 The products of palmyrah palm 2.6.1 Palmyrahjuice(Sap) 2.6.2 Toddy and sweet toddy 2
Cyanide and the human brain: perspectives from a model of food (cassava) poisoning
Annals of the New York Academy of Sciences, 2016
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 neurolog...
Cypermethrin [cyano-(3-phenoxyphenyl) methyl] 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carboxylate), second generation, type-II, pyrethroid insecticide having cyano group which has broad spectrum uses in agricultural sector. Present study aimed to investigate biochemical and histological changes induced by cypermethrin and protective effect of vitamin C in embryonic brain of developing chick of Gallus domestius. Fertilized eggs were divided into four groups having 30 eggs each. Group A: served as control, Group B: as vehicle which was administered with distilled water by immersion method, Group C: treatment group; was treated with 25 mg/ml of cypermethrin via immersion method and Group D: recovery group; supplemented with 25 mg/ml of cypermethrin along with 100 mg of vitamin C by air sac method. At embryonic day 0 (ED 0), all the groups treated with requisite doses for 60 minutes. Eggs were recovered and cerebellum was excised and further processed for biochemical and histological changes on embryonic day 16 (ED 16). The results of present study showed cypermethrin induced alterations in the general histology of cerebellum region of developing brain. Cypermethrin adversely affect different layers of cerebellum. Vacuolization was observed in the neurons of outer molecular layer, the middle layer of Purkinje cells showed devastating effects both on the nucleus and cytoplasm. Sign of pyknosis was observed in the nucleus of Purkinje cells whereas cytoplasm was found to be vacuolated. Innermost granular layer showed patchy loss of neurons. The results of light microscopy studies were further strengthened by biochemical studies. Several biochemical alterations were recorded in cypermethrin exposed developing brain. Cypermethrin treatment cause a decrease in protein content by 29.4% as compared to control group. The brain antioxidant marker enzymes such SOD, catalase and GSH were found to be decreased in treatment group as compared to control group and recovery group. The decreasing percentage of SOD, catalase, GSH was 35.75%, 39.16% and 37.43% respectively as compared to vitamin C protected group where estimated decreasing percentage was only 24.6%, 20.75%, 18% respectively. The MDA level was also increased to 115% as compared to vitamin C supplemented group where MDA level was increase to just 58.9%. Acetylcholinesterase, is a key marker enzyme which help in depicting toxicity level of xenobiotics. In the present study, the level of acetylcholinesterase enzyme was decreased to 62.15% as compared to control and vitamin C recovery group where estimated activity of this enzyme only decreased by 39.06% as compared to control group.
Cycads: evolutionary innovations and the role of plant-derived neurotoxins
Trends in plant science, 2003
Cycads are an important relic from the past and represent the oldest living seed plants. Cycads have been instrumental in our understanding the evolution of angiosperms and gymnosperms because they have recognizable morphological characteristics intermediate between less-recently evolved plants such as ferns and more-derived (advanced) plants including the angiosperms. Cycads also produce several compounds that are carcinogenic and neurotoxic. Because of their unique placement in terrestrial plant evolution, molecular studies should help to define the origins of structures that led to the rise of seed plants and the role of neurotoxic compounds that are found in cycads.
Toxicity Potential of Cyanogenic Glycosides in Edible Plants
Toxicity in Food [Working Title]
Cyanogenic glycosides are natural phytotoxins produced by over 2000 plant species, many of which are consumed by humans. The important food crops that contain cyanogenic glycosides include cassava (Manihot esculenta), sorghum (Sorghum bicolor), cocoyam (Colocasia esculenta L. and Xanthosoma sagittifolium L.), bamboo (Bambusa vulgaris), apple (Malus domestica), and apricot (Prunus armeniaca). Cyanogenic glycosides and their derivatives have amino acid-derived aglycones, which spontaneously degrade to release highly toxic hydrogen cyanide (HCN). Dietary cyanide exposure has been associated with several health challenges such as acute cyanide poisoning, growth retardation, and neurological disorders. This chapter will introduce general cyanogenesis principles, highlight major food plants with lethal cyanide levels, and provide epidemiological-based health conditions linked to cyanide intake. Furthermore, strategies for elimination of cyanogens from food crops, such as processing technologies, will be discussed. Finally, the chapter will analyze the role of cyanogenic plants in ensuring food security among resource-poor communities.