Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2024-12-27T12:41:22.917Z Has data issue: false hasContentIssue false
  • English
  • Français

New aspects in pathogenesis of konzo: neural cell damage directly caused by linamarin contained in cassava (Manihot esculenta Crantz)

Published online by Cambridge University Press:  09 March 2007

V. G. Sreeja ,
N. Nagahara ,
Q. Li  and
M. Minami
V. G. Sreeja
Affiliation:
Department of Environmental Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan
N. Nagahara*
Affiliation:
Department of Environmental Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan
Q. Li
Affiliation:
Department of Environmental Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan
M. Minami
Affiliation:
Department of Environmental Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan
*
*Corresponding author: Dr N. Nagahara, fax +81 3 5685 3054, email noriyuki@nms.ac.jp
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Epidemic spastic paraparesis (konzo) found in tropical and subtropical countries is known to be caused by long-term intake of cassava (Manihot esculenta Crantz), which contains a cyanoglucoside linamarin (α-hydroxyisobutyronitrile-β-D-glucopyranoside). It has been reported that linamarin is enzymatically converted to cyanide by bacteria in the intestine, and this is absorbed into the blood and then damages neural cells. However, unmetabolized linamarin was found in the urine after oral administration of cassava; thus, we hypothesized that konzo could be caused by direct toxicity of the unmetabolized linamarin that was transferred to the brain and could be transported into neural cells via a glucose transporter. In the present study it was confirmed that linamarin directly damaged neural culture pheochromocytoma cell (PC) 12 cells; 0·10 mM-linamarin caused cell death at 13·31 (SD 2·07) %, which was significantly different from that of control group (3·18 (SD 0·92) %, P=0·0004). Additional 10 μM-cytochalasin B, an inhibitor of a glucose transporter, prevented cell death: the percentage of dead cells significantly decreased to 6·06 (SD 1·98), P=0·0088). Furthermore, glucose also prevented cell death. These present results strongly suggest that linamarin competes with cytochalasin B and glucose for binding to a glucose transporter and enters into cells via glucose transporter.

Keywords

CassavaLinamarinKonzoGlucose transporter
Type
Research Article
Information
British Journal of Nutrition , Volume 90 , Issue 2 , August 2003 , pp. 467 - 472
Copyright
Copyright © The Nutrition Society 2003

References

Barrett, MD, Hill, DC, Alexander, JC & Zitnak, Z (1977) Fate of orally dosed linamarin in the rat. Can J Physiol Pharmacol 55, 134–136.Google Scholar
Bloch, R (1973) Inhibition of glucose transport in the human erythrocyte by cytochalasin B. Biochemistry 12, 4779–4801.Google Scholar
Brimer, L & Rosling, H (1993) A microdiffusion method with solid state detection of cyanogenic glycosides from cassava in human urine. Food Chem Toxicol 31, 599–603.CrossRefGoogle ScholarPubMed
Carlsson, L, Milingi Juma, A, Ronquist, G & Rosling, H (1999) Metabolic fates in humans of linamarin in cassava flour ingested as stiff porridge. Food Chem Toxicol 37, 307–312.CrossRefGoogle ScholarPubMed
Carlsson, L, Ronquist, G & Rosling, H (1995) A specific and sensitive method for the determination of linamarin in urine. Nat Toxins 3, 378–382.Google Scholar
Choi, IY, Lee, SP, Kim, SG & Gruetter, R (2001) In vivo measurements of brain glucose transport using the reversible Michaelis–Menten model and simultaneous measurements of cerebral blood flow changes during hypoglycemia. J Cereb Blood Flow Metab 21, 653–663.Google Scholar
Dauterive, R, Laroux, S, Bunn, RC, Chaisson, A, Sanson, T & Reed, BC (1996) C-terminal mutations that alter the turn over number for 3-O-methylglucose transport by GLUT1 and GLUT4. J Biol Chem 271, 11414–11421.CrossRefGoogle Scholar
Ellenhorn, MJ (1997) Cyanide poisoning. In Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed., pp. 1476–1482. [Ellenhorn, MJ, Schonwald, S, Ordog, G & Wasserberger, J, editors]. Baltimore: A. Waverly Company.Google Scholar
Gerhart, DZ, Levasseur, RJ, Broderius, MA & Drewes, LR (1989) Glucose transporter localization in brain using light and electron immunocytochemistry. J Neurosci Res 22, 464–472.CrossRefGoogle ScholarPubMed
Harrison, W & Gray, R (1972) Stimulaton of yeast hexokinase by catecholamines and related compounds. Arch Biochem Biophys 151, 357–360.CrossRefGoogle Scholar
Hernandez, T, Lundquist, P, Lourdes, O, Perez Cristi, R, Rodriguez, E & Rosling, H (1995) Fate in humans of dietary intake cyanogenic glycosides from root of sweet cassava consumed in Cuba. Nat Toxins 2, 114–117.CrossRefGoogle Scholar
Howlett, WP (1990) Konzo: A new human disease entity. Acta Hortic 375, 323–329.Google Scholar
Howlett, WP, Brubaker, GR, Mlingi, N & Rosling, H (1990) Konzo an upper motor neurone disease studied in Tanzania. Brain 113, 223–235.CrossRefGoogle ScholarPubMed
Kamalu, BP (1991) The effect of nutritionally balanced cassava (Manihot esculenta crantz) diet on endocrine functioning using the dog as experimental model 1. Pancreas. Brit J Nutr 65, 365–372.CrossRefGoogle ScholarPubMed
Kamalu, BP (1993) Pathological changes in growing dogs fed on a balanced cassava (Manihot escuenta crantz) diet. Brit J Nutr 69, 921–934.Google Scholar
Lancaster, PA, Ingram, JS, Lim, MY & Coursey, DG (1982) Traditional cassava-based foods: Survey of processing techniques. Econ Bot 36, 12–45.CrossRefGoogle Scholar
McAllister, MS, Krizanac-Bengez, L & Macchia, F (2001) Mechanisms of glucose transport at the blood–brain barrier: an in vitro study. Brain Res 904, 20–30.CrossRefGoogle ScholarPubMed
Macnamara, BP Estimation of toxicity of hydrolytic acid vapors in man. Edgewood Arsenal Technique Report EN-RT-76023, in Records of the US Marine Corps in the Pacific War.Google Scholar
Maduagwu, EN (1989) Metabolism of linamarin in rats. Food Chem Toxicol 7, 451–454.CrossRefGoogle Scholar
Maher, F, Davies-Hill, TM & Simpson, IA (1996) Substrate specificity and kinetic parameters of GLUT3 in rat cerebellar granule neurons. Biochem J 315, 1003–1011.Google Scholar
Maher, F, Vannucci, SJ & Simpson, IA (1994) Glucose transporter protein in brain. FASEB J 8, 1003–1011.CrossRefGoogle ScholarPubMed
Mancini, GM, Beerens, CE & Verheijen, FW (1990) Glucose transport in lysosomal membrane vesicles. Kinetic demonstration of a carrier for neutral hexoses. J Biol Chem 265, 12380–12387.CrossRefGoogle ScholarPubMed
Nagahara, N, Ito, T, Kitamura, H & Nishino, T (1998) Tissue and subcellular distribution of mercaptopyruvate sulfurtransferase in the rat: confocal laser fluorescence and immunoelectron microscopic studies combined with biochemical analysis. Histochem Cell Biol 110, 243–250.CrossRefGoogle ScholarPubMed
Nagahara, N, Ito, T & Minami, M (1999) Mercaptopyruvate sulfurtransferase as a defense against cyanide toxication: molecular properties and mode of detoxification. Histol Histopathol 14, 1277–1286.Google Scholar
Nagahara, N & Nishino, T (1996) Role of amino acid residues in the active site of rat liver mercaptopyruvate sulfurtransferase. J Biol Chem 271, 27395–27401.CrossRefGoogle ScholarPubMed
Nagahara, N, Okazaki, T & Nishino, T (1995) Cytosolic mercaptopyruvate Sulfurtransferase is evolutionarily related to mitochondrial rhodanese. J Biol Chem 270, 16230–16235.Google Scholar
Nagamatsu, S, Sawa, H, Kamada, K, Nakamichi, Y, Yoshimoto, K & Hoshino, T (1993) Neuron-specific glucose transporter (NGST) CNS distribution of GLUT3 rat glucose transporter (RGT3) in rat central neurons. FEBS Lett 334, 289–295.CrossRefGoogle Scholar
Simpson, IA, Vannucci, SJ, DeJoseph, MR & Hawkins, RA (2001) Glucose transporter asymmetries in the bovine blood–brain barrier. J Biol Chem 276, 12725–12729.CrossRefGoogle ScholarPubMed
Sunderesan, S, Nambisan, B & Eqswari Amna, CS (1987) Bitterness in cassava in relation to cyanoglucoside content. Indian J Agric Sci 53, 34–40.Google Scholar
Sörbo, SH (1953) Crystalline rhodanese, I. Purification and physicochemical examination. Acta Chem Scand 7, 1129–1136.CrossRefGoogle Scholar
Stahl, B, Wiesinger, H & Hamprecht, B (1989) Characterization of sorbitol uptake in rat glial primary cultures. J Neurochem 53, 665–671.CrossRefGoogle Scholar
Sylverster, DM & Sander, C (1990) Immunohistochemical localization of rhodanese. Histochem J 22, 197–200.CrossRefGoogle Scholar
Tylleskar, T, Banea, M, Bikangi, N, Cooke, PD, Poulter, NH & Rosling, H (1992) Cassava cyanogens and konzo, an upper motoneuron disease found in Africa. Lancet 339, 208–211.Google Scholar
Vannucci, SJ, Gibbs, EM & Simpson, IA (1997) Glucose utilization and glucose transporter proteins GLUT3 in brains of diabetic (db/db) mice. Am J Physiol 272, E267–E274.Google Scholar
Vannucci, SJ, Maher, F & Simpson, IA (1997) Glucose transporter proteins in the brain: Delivery of glucose to neurons and glia. Glia 21, 2–21.Google Scholar
Winkler, WO (1958) Report on method for glucosidal HCN in lima beans. J Assoc Agric Chem 41, 282–287.Google Scholar
Zeller, K, Duelli, R, Vogel, J, Schrock, H & Kuschinsky, W (1995) Autoradiographic analysis of the regional distribution of GLUT3 glucose transporters in the rat brain. Brain Res 698, 175–179.Google Scholar