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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 [email protected]
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Abstract

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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

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