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d-β-Hydroxybutyrate Prevents Glutamate-Mediated Lipoperoxidation and Neuronal Damage Elicited during Glycolysis Inhibition In Vivo

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Abstract

Excitotoxic neuronal death mediated by over-activation of glutamate receptors has been implicated in ischemia, hypoglycemia and some neurodegenerative diseases. It involves oxidative stress and is highly facilitated during impairment of energy metabolism. We have shown previously that in vivo systemic glycolysis inhibition with iodoacetate (IOA), exacerbates glutamate excitotoxicity. We have now investigated whether this effect involves oxidative damage to membrane lipids, as evaluated by the presence of thiobarbituric acid-reactive substances. We have also tested whether the ketone body, d-β-hydroxybutyrate (d-BHB), prevents lipoperoxidation and tissue damage. Results show that glutamate intrastriatal injection in control rats transiently enhances lipoperoxidation, while in IOA-treated animals increased lipoperoxidation is sustained. Treatment with d-BHB significantly reduces striatal lesions and lipoperoxidation. Vitamin E also reduced neuronal damage and lipoperoxidation. Results suggest that glycolysis impairment favors a pro-oxidant condition and situates oxidative damage as an important mediator of in vivo induced excitotoxicity. Results provide evidence for the neuroprotective effect of d-BHB against glutamate toxicity.

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Acknowledgments

This study was supported by 40306-M CONACYT and IN222503 PAPIIT UNAM grants to LM and CONACYT and DGEP-UNAM fellowships to JM.

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  1. Departamento de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, AP 70-253, 04510, Mexico D.F., Mexico

    Jana Mejía-Toiber, Teresa Montiel & Lourdes Massieu

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  1. Jana Mejía-Toiber
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  2. Teresa Montiel
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  3. Lourdes Massieu
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Correspondence to Lourdes Massieu.

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Mejía-Toiber, J., Montiel, T. & Massieu, L. d-β-Hydroxybutyrate Prevents Glutamate-Mediated Lipoperoxidation and Neuronal Damage Elicited during Glycolysis Inhibition In Vivo. Neurochem Res 31, 1399–1408 (2006). https://doi.org/10.1007/s11064-006-9189-5

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