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Genistein and daidzein induce neurotoxicity at high concentrations in primary rat neuronal cultures

  • Published:
Journal of Biomedical Science

Summary

It is known that estrogen can protect neurons from excitotoxicity. Since isoflavones possess estrogen-like activity, it is of interest to determine whether isoflavones can also protect neurons from glutamate-induced neuronal injury. Morphological observation and lactate dehydrogenase (LDH) release assay were used to estimate the cellular damage. It is surprising that, contrary to estrogen, isoflavones, specifically genistein and daidzein, are toxic to primary neuronal culture at high concentration. Treatment of neurons with 50 μM genistein and daidzein for 24 h increased LDH release by 90% and 67%, respectively, indicating a significant cellular damage. Under the same conditions, estrogen such as 17β-estradiol did not show any effect on primary culture of brain cells. At 100 μM, both genistein and daidzein increased LDH release by 2.6- and 3-fold, respectively with a 30-min incubation. Furthermore, both genistein and daidzein at 50 μM increased the intracellular calcium level, [Ca2+]i, significantly. To determine their mode of action, genistein and daidzein were tested on glutamate and GABAA receptor binding. Both genistein and daidzein were found to have little effect on glutamate receptor binding, while the binding of [3H]muscimol to GABAA receptors was markedly inhibited. However, 17β-estradiol did not affect GABAA receptor binding suggesting that the toxic effect of genistein and daidzein could be due to their inhibition of the GABAA receptor resulting in further enhancement of excitation by glutamate and leading to cellular damage.

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Acknowledgements

This work was supported in part by National Institutes of Health Grant NS37851, National Science Foundation Grant IBN-9723079, and the Schmidt Family Foundation at Florida Atlantic University. We would like to thank Wanda Dominger for excellent assistance in editing of the manuscript.

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Authors and Affiliations

  1. Department of Biomedical Science, Florida Atlantic University, Boca Raton, FL, 33431, USA

    Ying Jin, Heng Wu, Eric M. Cohen, Jianning Wei, Howard Prentice & Jang-Yen Wu

  2. Complex System and Brain Sciences, Florida Atlantic University, Boca Raton, FL, 33431, USA

    Heng Wu & Jang-Yen Wu

  3. Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, 66045, USA

    Hong Jin

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  1. Ying Jin
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  2. Heng Wu
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  3. Eric M. Cohen
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Correspondence to Heng Wu.

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Ying Jin, Heng Wu contributed equally to this article.

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Jin, Y., Wu, H., Cohen, E.M. et al. Genistein and daidzein induce neurotoxicity at high concentrations in primary rat neuronal cultures. J Biomed Sci 14, 275–284 (2007). https://doi.org/10.1007/s11373-006-9142-2

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  • DOI: https://doi.org/10.1007/s11373-006-9142-2

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