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Neurotoxicity and pharmacology of Lathyrus sativus extracts of high- and low-toxicity strains

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Abstract

Neurolathyrism is characterized by spastic paraparesis of the legs. It is caused by overconsumption of grass pea (Lathyrus sativus L.; Leguminosae). We studied toxicity of extracts of L. sativus seeds from two different areas—Bangladesh and Canada—toward rat primary neuron/glia culture. Both extracts showed acute neurotoxicity within 24 h when the 75% ethanol extracts were added to the neuron/glia culture. Fractionation of the extracts showed that the water-soluble fraction accounted for ca. 75–84% of total toxicity in which 3-N-oxalyl-l-2,3-diaminopropanoic acid (l-β-ODAP) was present at the highest concentration. Toxicity of the water-soluble fraction obtained from Bangladeshi seeds was significantly higher than that obtained from Canada. Effects of these fractions were reversed almost completely by 1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzo[f]quinoxaline-7-sulfonamide (NBQX), an antagonist of AMPA-receptor. They were partially reversed by group I metabotropic glutamate receptor antagonists (RS)-1-aminoindan-1,5-dicarboxylic acid, or (S)-α-methyl-4-carboxyphenyl-glycine [(S)-MCPG]. Nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) strongly decreased the extracts’ toxicity. These data show that the neurotoxicity of grass pea seeds is attributable to l-β-ODAP, the toxicity of which is mediated by collective effects of l-β-ODAP on the AMPA-type receptor, metabotropic glutamate receptors, and NO production.

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Acknowledgements

This work was supported by the ‘Academic Frontier’ Project for Private Universities matching-fund subsidy from Ministry of Education, Culture, Sports, Science and Technology, 2002–2006. We are grateful to Prof. F. Lambein, Ghent University, Belgium, for providing grass pea seeds. We are grateful to Ms. B.S. Tomoe Higashino and Ms. B.S. Junko Akasaka for technical assistance.

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Authors and Affiliations

  1. Laboratory of Molecular Cell Biology, College of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi 274-8555, Japan

    Kuniko Kusama-Eguchi, Atsuhiro Suda, Yoshio Ogawa & Kazuko Watanabe

  2. Center for Environment, Health and Field Sciences, Chiba University, 6-2-1 Kashiwanoha, Kashiwa 277-0882, Japan

    Fumio Ikegami

  3. Laboratory of Physiology and Anatomy, College of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi 274-8555, Japan

    Tadashi Kusama

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  1. Kuniko Kusama-Eguchi
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  2. Atsuhiro Suda
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  3. Fumio Ikegami
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  4. Tadashi Kusama
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  5. Yoshio Ogawa
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  6. Kazuko Watanabe
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Correspondence to Kuniko Kusama-Eguchi.

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Kusama-Eguchi, K., Suda, A., Ikegami, F. et al. Neurotoxicity and pharmacology of Lathyrus sativus extracts of high- and low-toxicity strains. J Nat Med 60, 107–112 (2006). https://doi.org/10.1007/s11418-005-0020-4

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  • DOI: https://doi.org/10.1007/s11418-005-0020-4

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